AbstractTransfusion dependent β-thalassemia is a genetic blood disorder characterized by chronic anaemia. Blood transfusion is lifesaving but comes at a cost. Iron overload emerges as a prime culprit as a free radicals damage endothelial cells. Chronic anaemia further disrupts oxygen delivery, exacerbating the oxidative stress.

摘要输血依赖性β地中海贫血是一种以慢性贫血为特征的遗传性血液疾病。输血可以挽救生命，但要付出代价。。慢性贫血进一步破坏氧气输送，加剧氧化应激。

Increased levels of met-haemoglobin and malondialdehyde compromise endothelial function. This research sheds light on the impact of met-haemoglobin and oxidative stress on endothelial function in 50 patients with transfusion dependent β-thalassemia major compared to 50 healthy individuals as control.

met血红蛋白和丙二醛水平升高会损害内皮功能。这项研究揭示了met血红蛋白和氧化应激对50例输血依赖性β地中海贫血患者内皮功能的影响，而50例健康人作为对照。

Blood samples were collected & subjected to CBC, biochemical analysis including creatinine, ferritin, CRP, LDH, and HCV antibodies. Oxidative stress was assessed using met-haemoglobin & malondialdehyde. Endothelial dysfunction was evaluated by endothelial activation and stress index (EASIX). EASIX, met-haemoglobin and malondialdehyde were significantly increased in patients (1.44 ± 0.75, 2.07 ± 0.2, 4.8 ± 0.63; respectively) compared to the control (0.52 ± 0.24,0.88 ± 0.34,0.8 ± 0.34; respectively).

收集血样并进行CBC，生化分析，包括肌酐，铁蛋白，CRP，LDH和HCV抗体。使用met血红蛋白和丙二醛评估氧化应激。通过内皮激活和应激指数（EASIX）评估内皮功能障碍。EASIX，met血红蛋白和丙二醛在患者中显着增加（1.44±0.75,2.07±0.2,4.8±0.63；（分别为0.52±0.24,0.88±0.34,0.8±0.34；分别）。

Significant strong positive correlation was found between EASIX and met-haemoglobin, malondialdehyde, serum ferritin and CRP (P = 0.00, r = 0.904, P = 0.00, r = 0.948, P = 0.00, r = 0.772, P = 0.00, r = 0.971; respectively. Met-haemoglobin as well as EASIX should be routinely estimated to assess endothelial function especially before the decision of splenectomy.

EASIX与met血红蛋白、丙二醛、血清铁蛋白和CRP呈显著正相关（P=0.00，r=0.904，P=0.00，r=0.948，P=0.00，r=0.772，P=0.00，r=0.971）（a）；分别。应常规评估Met血红蛋白和EASIX，以评估内皮功能，尤其是在决定脾切除术之前。

Antioxidant drugs should be supplemented..

应补充抗氧化药物。。

Introductionβ-thalassemia is a major monogenic disease with reduced or absent β globin genes1. The unpaired α-globin gene results in chronic haemolysis and ineffective erythropoiesis necessitating lifelong blood transfusion. This exposes the patients to many complications namely; chronic anaemia, iron overload, oxidative stress, hypercoagulability and platelet activation in which damaged endothelial cells will be the end sequence2,3.The normal endothelium serves as a critical regulator of vascular homeostasis, maintaining a delicate equilibrium between diverse physiological processes.

引言β地中海贫血是一种主要的单基因疾病，β珠蛋白基因减少或缺失1。未配对的α-珠蛋白基因导致慢性溶血和无效的红细胞生成，需要终身输血。这使患者面临许多并发症，即：；慢性贫血，铁超负荷，氧化应激，高凝状态和血小板活化，其中受损的内皮细胞将是最终序列2,3。正常内皮作为血管稳态的关键调节剂，在不同生理过程之间保持微妙的平衡。

These include vasomotor function (dilation and constriction), vascular smooth muscle cell growth and death, a balanced release of pro- and anti-inflammatory mediators, and the delicate interplay of oxidative stress and antioxidant defense4. Chronic haemolysis in transfusion-dependent β-thalassemia (TDT) is a key driver of inflammation as red blood cells destruction releases inflammatory mediators that can lead to oxidative stress, immune system activation, and iron overload5.

这些包括血管舒缩功能（扩张和收缩），血管平滑肌细胞的生长和死亡，促炎和抗炎介质的平衡释放，以及氧化应激和抗氧化防御的微妙相互作用4。输血依赖性β地中海贫血（TDT）中的慢性溶血是炎症的关键驱动因素，因为红细胞破坏会释放可导致氧化应激，免疫系统激活和铁超载的炎症介质5。

A relationship between inflammatory biomarkers and thalassemia has been recently reported6. Inflammation makes endothelium to undergo multiple functional modifications that are adaptive but become harmful when exceeding, leading to microvascular dysfunction and multiorgan failure7. Moreover; the endothelial dysfunction is caused by the interplay of adhesion molecules and inflammatory cytokines such soluble intercellular adhesion molecule and E-selectin8,9.Oxidative stress in TDT patients is caused mostly by excess non-transferrin bound iron, a powerful free radical that destroys organs, DNA and mitochondria.

最近报道了炎症生物标志物与地中海贫血之间的关系6。炎症使内皮细胞经历多种适应性功能修饰，但超过时会变得有害，导致微血管功能障碍和多器官衰竭7。；内皮功能障碍是由粘附分子和炎性细胞因子如可溶性细胞间粘附分子和E-选择素8,9的相互作用引起的。TDT患者的氧化应激主要是由过量的非转铁蛋白结合铁引起的，这是一种破坏器官，DNA和线粒体的强大自由基。

TDT patients are likely to have simultaneous intravascular haemolysis when subjected to oxidative stress which .

TDT患者在遭受氧化应激时可能同时发生血管内溶血。

Data availability

数据可用性

All data supporting the findings of this study are available within the paper and its Supplementary Information. All main data are available upon request. If someone wants to request data from this study you can contact the corresponding author: Maha Abubakr Feissal Rabie, Email: maha.feissal@pua.edu.eg, Mobile number: 0122230469, Fax number: 033877000.

本文及其补充信息中提供了支持本研究结果的所有数据。所有主要数据均可根据要求提供。maha.feissal@pua.edu.eg，手机号码：0122230469，传真号码：033877000。

Address: Pharos University, Canal El Mahmoudia Street, beside Green Plaza Complex, Alexandria, Egypt..

地址：埃及亚历山大市绿色广场综合楼旁边的Canal El Mahmoudia Street Pharos大学。。

ReferencesShang, X. & Xu, X. Update in the genetics of thalassemia: What clinicians need to know. Best Pract. Res. Clin. Obstet. Gynaecol. 39, 3–15. https://doi.org/10.1016/j.bpobgyn.2016.10.012 (2017).Article

ReferenceShang，X。＆Xu，X。地中海贫血遗传学的最新进展：临床医生需要知道什么。最佳实践。临床研究。障碍。妇科。39，3-15。https://doi.org/10.1016/j.bpobgyn.2016.10.012（2017年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Fibach, E. & Dana, M. Oxidative stress in β-thalassemia. Mol. Diagn. Ther. 23, 245–261. https://doi.org/10.1007/s40291-018-0373-5 (2019).Article

Fibach，E。＆Dana，M。β-地中海贫血中的氧化应激。。他们。23245-261。https://doi.org/10.1007/s40291-018-0373-5（2019年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Abdolalian, M., Zarif, M. N. & Javan, M. The role of extracellular vesicles on the occurrence of clinical complications in β-thalassemia. Exp. Hematol. 127, 28–39. https://doi.org/10.1016/j.exphem.2023.08.009 (2023).Article

Abdolalian，M.，Zarif，M.N。＆Javan，M。细胞外囊泡在β地中海贫血临床并发症发生中的作用。实验血液学。127，28-39。https://doi.org/10.1016/j.exphem.2023.08.009（2023年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Higashi, Y. Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease. Antioxidants (Basel) 11. https://doi.org/10.3390/antiox11101958 (2022).Dimitrov, J. D., Roumenina, L. T., Perrella, G. & Rayes, J. Basic mechanisms of hemolysis-associated thrombo-inflammation and immune dysregulation.

Higashi，Y。氧化应激和炎症在血管内皮功能障碍相关疾病中的作用。抗氧化剂（巴塞尔）11。https://doi.org/10.3390/antiox11101958（2022年）。。

Arterioscler. Thromb. Vasc. Biol. 43, 1349–1361. https://doi.org/10.1161/atvbaha.123.318780 (2023).Article .

动脉硬化。血栓。Vasc。生物学431349-1361。https://doi.org/10.1161/atvbaha.123.318780（2023年）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Caprari, P. et al. Hemorheological profiles and chronic inflammation markers in transfusion-dependent and non-transfusion- dependent thalassemia. Front. Mol. Biosci. 9, 1108896. https://doi.org/10.3389/fmolb.2022.1108896 (2022).Article

Caprari，P。等。输血依赖性和非输血依赖性地中海贫血的血液流变学特征和慢性炎症标志物。正面。摩尔生物科学。91108896年。https://doi.org/10.3389/fmolb.2022.1108896（2022年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Joffre, J. & Hellman, J. Oxidative stress and endothelial dysfunction in sepsis and acute inflammation. Antioxid. Redox. Signal. 35, 1291–1307. https://doi.org/10.1089/ars.2021.0027 (2021).Article

Joffre，J。＆Hellman，J。脓毒症和急性炎症中的氧化应激和内皮功能障碍。抗氧化剂。氧化还原。信号。351291-1307年。https://doi.org/10.1089/ars.2021.0027（2021年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pallewar, T. S., Sharma, K., Sharma, S., Chandra, J. & Nangia, A. Endothelial activation markers in polytransfused children with beta thalassemia: Study from a Tertiary Care Centre in India. Indian J. Hematol. Blood Transfus. 38, 178–183. https://doi.org/10.1007/s12288-021-01471-4 (2022).Article .

Pallewar，T.S.，Sharma，K.，Sharma，S.，Chandra，J。＆Nangia，A。β地中海贫血多输血儿童的内皮激活标志物：来自印度三级保健中心的研究。印度J.Hematol。输血。38178-183。https://doi.org/10.1007/s12288-021-01471-4（2022年）。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Liu, X. & Spolarics, Z. Methemoglobin is a potent activator of endothelial cells by stimulating IL-6 and IL-8 production and E-selectin membrane expression. Am. J. Physiol. Cell Physiol. 285, C1036-1046. https://doi.org/10.1152/ajpcell.00164.2003 (2003).Article

Liu，X。＆Spolarics，Z。高铁血红蛋白通过刺激IL-6和IL-8的产生以及E-选择素膜的表达而成为内皮细胞的有效激活剂。Am.J.Physiol。细胞生理学。285，C1036-1046。https://doi.org/10.1152/ajpcell.00164.2003（2003年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hirsch, R. E., Sibmooh, N., Fucharoen, S. & Friedman, J. M. HbE/β-thalassemia and oxidative stress: The key to pathophysiological mechanisms and novel therapeutics. Antioxid. Redox. Signal 26, 794–813. https://doi.org/10.1089/ars.2016.6806 (2017).Article

Hirsch，R.E.，Sibmooh，N.，Fucharoen，S。＆Friedman，J.M。HbE/β-地中海贫血和氧化应激：病理生理机制和新疗法的关键。抗氧化剂。氧化还原。信号26794–813。https://doi.org/10.1089/ars.2016.6806（2017年）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bamm, V. V., Henein, M. E. L., Sproul, S. L. J., Lanthier, D. K. & Harauz, G. Potential role of ferric hemoglobin in MS pathogenesis: Effects of oxidative stress and extracellular methemoglobin or its degradation products on myelin components. Free Radic. Biol. Med. 112, 494–503. https://doi.org/10.1016/j.freeradbiomed.2017.08.022 (2017).Article .

Bamm，V.V.，Henein，M.E.L.，Sproul，S.L.J.，Lanthier，D.K。＆Harauz，G。铁血红蛋白在MS发病机制中的潜在作用：氧化应激和细胞外高铁血红蛋白或其降解产物对髓鞘成分的影响。自由基。生物医学112494-503。https://doi.org/10.1016/j.freeradbiomed.2017.08.022（2017年）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pagan, L. U., Gomes, M. J., Martinez, P. F. & Okoshi, M. P. Oxidative stress and heart failure: Mechanisms, signalling pathways, and therapeutics. Oxid. Med. Cell. Longev. 2022, 9829505. https://doi.org/10.1155/2022/9829505 (2022).Article

Pagan，L.U.，Gomes，M.J.，Martinez，P.F。和Okoshi，M.P。氧化应激和心力衰竭：机制，信号通路和治疗。氧化剂。医学细胞。朗格夫。20229829505年。https://doi.org/10.1155/2022/9829505（2022年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Shaito, A. et al. Oxidative stress-induced endothelial dysfunction in cardiovascular diseases. Front. Biosci. 27, 105. https://doi.org/10.31083/j.fbl2703105 (2022).Ali, S. et al. Current status of beta-thalassemia and its treatment strategies. Mol. Genet. Genomic. Med. 9, e1788. https://doi.org/10.1002/mgg3.1788 (2021).Article .

Shaito，A。等人。心血管疾病中氧化应激诱导的内皮功能障碍。正面。生物科学。27105页。https://doi.org/10.31083/j.fbl2703105（2022年）。Ali，S.等人。β地中海贫血的现状及其治疗策略。分子遗传学。基因组学。医学9，e1788。https://doi.org/10.1002/mgg3.1788（2021年）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chennupati, R. et al. Chronic anemia is associated with systemic endothelial dysfunction. Front. Cardiovasc. Med. 10, 1099069. https://doi.org/10.3389/fcvm.2023.1099069 (2023).Article

Chennupati，R。等人。慢性贫血与全身内皮功能障碍有关。正面。心血管。医学101099069。https://doi.org/10.3389/fcvm.2023.1099069（2023年）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Meegan, J. E., Bastarache, J. A. & Ware, L. B. Toxic effects of cell-free hemoglobin on the microvascular endothelium: Implications for pulmonary and nonpulmonary organ dysfunction. Am. J. Physiol. Lung Cell Mol. Physiol. 321, L429-l439. https://doi.org/10.1152/ajplung.00018.2021 (2021).Article .

Meegan，J.E.，Bastarache，J.A。＆Ware，L.B。无细胞血红蛋白对微血管内皮的毒性作用：对肺和非肺器官功能障碍的影响。Am.J.Physiol。肺细胞分子生理学。321，L429-l439。https://doi.org/10.1152/ajplung.00018.2021（2021年）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cyr, A. R., Huckaby, L. V., Shiva, S. S. & Zuckerbraun, B. S. Nitric oxide and endothelial dysfunction. Crit. Care Clin. 36, 307–321. https://doi.org/10.1016/j.ccc.2019.12.009 (2020).Article

Cyr，A.R.，Huckaby，L.V.，Shiva，S.S。＆Zuckerbraun，B.S。一氧化氮和内皮功能障碍。暴击。护理临床。36307-321。https://doi.org/10.1016/j.ccc.2019.12.009（2020年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lal, A. Challenges in chronic transfusion for patients with thalassemia. Hematol. Am. Soc. Hematol. Educ. Program. 2020, 160–166. https://doi.org/10.1182/hematology.2020000102 (2020).Article

Lal，A。地中海贫血患者慢性输血的挑战。血液学。美国血液学会。教育。。2020年，160-166年。https://doi.org/10.1182/hematology.2020000102（2020年）。文章

Google Scholar

谷歌学者

Sposi, N. M. Beta Thalassemia; Oxidative Stress and Iron Overload in β-Thalassemia: An Overview (2019).Sovira, N. et al. Effects of α-tocopherol on hemolysis and oxidative stress markers on red blood cells in β-thalassemia major. Clin. Exp. Pediatr. 63, 314–320. https://doi.org/10.3345/cep.2019.00542 (2020).Article .

Sposi，N.M。β地中海贫血；β地中海贫血中的氧化应激和铁超负荷：概述（2019）。Sovira，N.等人。α-生育酚对重型β地中海贫血患者红细胞溶血和氧化应激标志物的影响。临床。实验儿科。63314-320。https://doi.org/10.3345/cep.2019.00542（2020年）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barclay, J. A., Ziemba, S. E. & Ibrahim, R. B. Dapsone-induced methemoglobinemia: A primer for clinicians. Ann. Pharmacother. 45, 1103–1115. https://doi.org/10.1345/aph.1Q139 (2011).Article

Barclay，J.A.，Ziemba，S.E。和Ibrahim，R.B。氨苯砜诱导的高铁血红蛋白血症：临床医生的入门读物。安。药剂师。451103-1115年。https://doi.org/10.1345/aph.1Q139（2011年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Tandon, V. R. et al. Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India. Indian J. Med. Res. 142, 33–39. https://doi.org/10.4103/0971-5916.162093 (2015).Article

Tandon，V.R.等人，《药物引起的疾病（DIDs）：印度一家三级保健教学医院的经验》。《印度医学杂志》第142号，第33-39页。https://doi.org/10.4103/0971-5916.162093（2015年）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Varma, A. et al. Endothelial Activation and Stress Index (EASIX) at admission predicts fluid overload in recipients of allogeneic stem cell transplantation. Biol. Blood Marrow Transplant. 26, 1013–1020. https://doi.org/10.1016/j.bbmt.2020.01.028 (2020).Article

Varma，A。等人。入院时的内皮激活和应激指数（EASIX）预测异基因干细胞移植受者的液体超负荷。生物学。骨髓移植。261013-1020年。https://doi.org/10.1016/j.bbmt.2020.01.028（2020年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Feissal Rabie, M. A., Gaber, M. H., Soula, M. A. & Masoud, I. M. Endothelail and stress index as one of new prognostic determinants of COVID- 19 severity. Afro-Egypt. J. Infecti. Endemic Dis. 13, 101–113. https://doi.org/10.21608/aeji.2023.206428.1287 (2023).Jameson, J. L. et al. in Harrison’s Principles of Internal Medicine, 20e Ch.

Feissal-Rabie，M.A.，Gaber，M.H.，Soula，M.A.＆Masoud，I.M.Endothelail和应激指数是新型冠状病毒肺炎严重程度的新预后决定因素之一。非洲裔埃及。J、 感染。地方病。13101-113。https://doi.org/10.21608/aeji.2023.206428.1287（2023年）。Jameson，J.L.等人，《哈里森内科学原理》，20e Ch。

299, e1-e8 (McGraw-Hill Education, 2018).Kowalczyk, P. et al. Mitochondrial oxidative stress—A causative factor and therapeutic target in many diseases. Int. J. Mol .Sci. 22. https://doi.org/10.3390/ijms222413384 (2021).Ayyash, H. & Sirdah, M. Hematological and biochemical evaluation of β-thalassemia major (βTM) patients in Gaza Strip: A cross-sectional study.

299，e1-e8（McGraw-Hill Education，2018）。Kowalczyk，P。等。线粒体氧化应激-许多疾病的致病因素和治疗靶点。内景J.摩尔。。22https://doi.org/10.3390/ijms222413384（2021年）。Ayyash，H。＆Sirdah，M。加沙地带β地中海贫血（βTM）患者的血液学和生化评估：一项横断面研究。

Int. J. Health Sci. 12, 18–24 (2018)..

Int.J.健康科学。12、18–24（2018年）。。

Google Scholar

谷歌学者

Aldwaik, R. et al. Health status of patients with β-thalassemia in the West Bank: A retrospective-cohort study. Front. Med . 8, 788758. https://doi.org/10.3389/fmed.2021.788758 (2021).Solangi, D. A. et al. Blood chemistry (hematology) of transfusion dependent Beta thalassemia patients at hyderabad and adjoining areas.

Aldwaik，R.等人，《西岸β地中海贫血患者的健康状况：一项回顾性队列研究》。正面。医学。8788758人。https://doi.org/10.3389/fmed.2021.788758（2021年）。Solangi，D.A.等人，《海得拉巴及其邻近地区输血依赖型β地中海贫血患者的血液化学（血液学）。

2018 19, 5. https://doi.org/10.21743/pjaec/2018.06.09 (2018).Sande, C. et al. Impact of splenectomy on postsurgical platelet count. Am. J. Clin. Pathol. 152, S24–S25. https://doi.org/10.1093/ajcp/aqz112.047 (2019).Article .

2018年19月5日。https://doi.org/10.21743/pjaec/2018.06.09（2018年）。Sande，C.等人。脾切除术对术后血小板计数的影响。美国J.克林。病理学。152，S24-S25。https://doi.org/10.1093/ajcp/aqz112.047（2019年）。文章。

Google Scholar

谷歌学者

Basu, D., Adhya, D. G., Sinha, R. & Chakravorty, N. Role of malonaldehyde as a surrogate biomarker for iron overload in the β-thalassemia patient: A systematic meta-analysis. Adv. Redox. Res. 3, 100017. https://doi.org/10.1016/j.arres.2021.100017 (2021).Article

Basu，D.，Adhya，D.G.，Sinha，R。＆Chakravorty，N。丙二醛作为β地中海贫血患者铁超负荷替代生物标志物的作用：系统荟萃分析。高级氧化还原。第310017号决议。https://doi.org/10.1016/j.arres.2021.100017（2021年）。文章

CAS

中科院

Google Scholar

谷歌学者

Neaimy, K. S. A., Alkhyatt, M. M. & Jarjess, I. A. New insights of oxidative stress and thalassemia may lead to antioxidant therapy. Pharmacognosy J. (2024).Al-Hakeim, H. K., Auda, F. M. & Ali, B. M. Lack of correlation between non-labile iron parameters, total carbonyl and malondialdehyde in major thalassemia.

Neaimy，K.S.A.，Alkhyatt，M.M。和Jarjess，I.A。对氧化应激和地中海贫血的新见解可能会导致抗氧化治疗。生药学J.（2024）。Al-Hakeim，H.K.，Auda，F.M。和Ali，B.M。在主要地中海贫血中，非不稳定铁参数，总羰基和丙二醛之间缺乏相关性。

J. Clin. Biochem. Nutr. 55, 203–206. https://doi.org/10.3164/jcbn.14-24 (2014).Article .

J.克林顿。生物化学。纳特。55, 203–206.https://doi.org/10.3164/jcbn.14-24(2014).第条。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fatima, T. et al. Oxidative stress in Beta-thalassemia Patients: Role of enzymatic and non-enzymatic modulators. Protein Pept. Lett. 30, 1030–1037. https://doi.org/10.2174/0109298665246270231020062048 (2023).Article

Fatima，T。等。β地中海贫血患者的氧化应激：酶和非酶调节剂的作用。蛋白质Pept。利特。301030-1037年。https://doi.org/10.2174/0109298665246270231020062048（2023年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Jarisch, A. et al. Serum ferritin is not a reliable predictor to determine iron overload in thalassemia major patients post-hematopoietic stem cell transplantation. Eur. J. Haematol. 101, 791–797. https://doi.org/10.1111/ejh.13169 (2018).Article

Jarisch，A。等人。血清铁蛋白不是确定造血干细胞移植后地中海贫血主要患者铁超负荷的可靠预测指标。欧洲血液学杂志。101791-797。https://doi.org/10.1111/ejh.13169（2018年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Shah, F. et al. Relationship between serum ferritin and outcomes in β-Thalassemia: A systematic literature review. J. Clin. Med. 11. https://doi.org/10.3390/jcm11154448 (2022).Balbaa, O. A., Kamel, M. A., Salem, K. S. & Sadek, N. A. Impact of haptoglobin gene polymorphism on phenotypic variability in β-thalassemia patients: relation to iron overload and oxidative stress.

Shah，F。等人。血清铁蛋白与β地中海贫血预后的关系：系统文献综述。J、 临床。医学11。https://doi.org/10.3390/jcm11154448（2022年）。Balbaa，O.A.，Kamel，M.A.，Salem，K.S。＆Sadek，N.A。触珠蛋白基因多态性对β地中海贫血患者表型变异性的影响：与铁超负荷和氧化应激的关系。

Afro-Egypt. J. Infect. Endemic Dis. 13, 181–189. https://doi.org/10.21608/aeji.2023.220501.1299 (2023).Garbowski, M. W. et al. Luspatercept stimulates erythropoiesis, increases iron utilization, and redistributes body iron in transfusion-dependent thalassemia. Am. J. Hematol. 99, 182–192. https://doi.org/10.1002/ajh.27102 (2024).Article .

非洲裔埃及。J、 感染。地方病。13181-189年。https://doi.org/10.21608/aeji.2023.220501.1299（2023年）。Garbowski，M。W。等人。Luspatercept刺激红细胞生成，增加铁的利用率，并在输血依赖性地中海贫血中重新分配体内铁。美国血液学杂志。99182-192。https://doi.org/10.1002/ajh.27102（2024年）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Luft, T. et al. EASIX in patients with acute graft-versus-host disease: A retrospective cohort analysis. Lancet Haematol. 4, e414–e423. https://doi.org/10.1016/s2352-3026(17)30108-4 (2017).Article

。柳叶刀血液。4，e414–e423。https://doi.org/10.1016/s2352-3026（17） 30108-4（2017）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Scioli, M. G. et al. Oxidative stress and new pathogenetic mechanisms in endothelial dysfunction: Potential diagnostic biomarkers and therapeutic targets. J. Clin. Med. 9. https://doi.org/10.3390/jcm9061995 (2020).Rebbani, K. & Tsukiyama-Kohara, K. HCV-induced oxidative stress: Battlefield-winning strategy.

Scioli，M.G.等。氧化应激和内皮功能障碍的新发病机制：潜在的诊断生物标志物和治疗靶点。J、 临床。医学9。https://doi.org/10.3390/jcm9061995（2020年）。Rebbani，K。＆Tsukiyama Kohara，K。HCV诱导的氧化应激：战场胜利策略。

Oxid. Med. Cell Longev. 2016, 7425628. https://doi.org/10.1155/2016/7425628 (2016).Article .

氧化物。医学细胞Longev。2016, 7425628.https://doi.org/10.1155/2016/7425628(2016).第条。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Almaeen, A. H. et al. Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients. Arch. Med. Sci. 17, 368–375. https://doi.org/10.5114/aoms.2019.91451 (2021).Article

Almaeen，A.H.等人，《丙型肝炎初治和肝硬化患者的氧化应激、免疫和细胞缺氧生物标志物》。拱门。医学科学。17368-375。https://doi.org/10.5114/aoms.2019.91451（2021年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hanafy, A. S., Basha, M. A. K. & Wadea, F. M. Novel markers of endothelial dysfunction in hepatitis C virus-related cirrhosis: More than a mere prediction of esophageal varices. World J. Hepatol. 12, 850–862. https://doi.org/10.4254/wjh.v12.i10.850 (2020).Article

Hanafy，A.S.，Basha，M.A.K.＆Wadea，F.M。丙型肝炎病毒相关性肝硬化内皮功能障碍的新标志物：不仅仅是食管静脉曲张的预测。世界J.Hepatol。12850–862。https://doi.org/10.4254/wjh.v12.i10.850（2020年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Farmakis, D. et al. 2021 Thalassaemia International Federation Guidelines for the management of transfusion-dependent thalassemia. Hemasphere 6, e732. https://doi.org/10.1097/hs9.0000000000000732 (2022).Article

Farmakis，D.等人，《2021地中海贫血国际联合会输血依赖性地中海贫血管理指南》。Hemasphere 6，e732。https://doi.org/10.1097/hs9.0000000000000732（2022年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rawi, S. & Wu, G. Y. Pathogenesis of thrombocytopenia in chronic HCV infection: A review. J. Clin. Transl. Hepatol. 8, 184–191. https://doi.org/10.14218/jcth.2020.00007 (2020).Kedia, S. et al. Benign and malignant hematological manifestations of chronic hepatitis C virus infection. Int.

Rawi，S。＆Wu，G.Y。慢性HCV感染中血小板减少症的发病机制：综述。J、 临床。翻译。肝病。8184-191年。https://doi.org/10.14218/jcth.2020.00007（2020年）。Kedia，S.等人。慢性丙型肝炎病毒感染的良性和恶性血液学表现。内景。

J. Prev. Med. 5, S179-192 (2014).PubMed .

J.上一篇。医学5，S179-192（2014）。PubMed。

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Abozeid, F., Shaaban, Y., Elbogdady, M. & Jamal, E. Evaluation of hepatic toxicity in autoimmune hemolytic anemia (AIHA) and Evans syndrome patients: A single-center Egyptian study. Egypt. J. Internal Med. 36, 22. https://doi.org/10.1186/s43162-024-00279-8 (2024).Article

Abozeid，F.，Shaaban，Y.，Elbogdady，M。＆Jamal，E。评估自身免疫性溶血性贫血（AIHA）和Evans综合征患者的肝毒性：一项单中心埃及研究。埃及。J、 内部医学36,22。https://doi.org/10.1186/s43162-024-00279-8（2024年）。文章

Google Scholar

谷歌学者

Kedia, S. et al. Splenectomy in cirrhosis with hypersplenism: Improvement in cytopenias, Child’s status and institution of specific treatment for hepatitis C with success. Ann. Hepatol. 11, 921–929 (2012).Article

Kedia，S.等人，《肝硬化脾功能亢进的脾切除术：血细胞减少、儿童状况的改善以及丙型肝炎特异性治疗的成功制定》。安。希沃特。11921-929（2012）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Akhtari, M., Curtis, B. & Waller, E. K. Autoimmune neutropenia in adults. Autoimmun. Rev. 9, 62–66. https://doi.org/10.1016/j.autrev.2009.03.006 (2009).Article

Akhtari，M.，Curtis，B。＆Waller，E.K。成人自身免疫性中性粒细胞减少症。自身免疫。第9版，第62-66页。https://doi.org/10.1016/j.autrev.2009.03.006。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Abou El Azm, A. R. et al. Correlation of viral load with bone marrow and hematological changes in pale patients with chronic hepatitis C virus. Arch. Virol. 157, 1579–1586. https://doi.org/10.1007/s00705-012-1321-z (2012).Aref, S. et al. Neutrophil apoptosis in neutropenic patients with hepatitis C infection: Role of Caspases 3, 10, and GM-CSF.

Abou El Azm，A.R.等人。慢性丙型肝炎病毒苍白患者病毒载量与骨髓和血液学变化的相关性。拱门。维罗尔。1571579-1586年。https://doi.org/10.1007/s00705-012-1321-z。。

Indian J. Hematol. Blood Transfus. 27, 81–87. https://doi.org/10.1007/s12288-011-0067-1 (2011).Article .

印度J.Hematol。输血。27，81-87。https://doi.org/10.1007/s12288-011-0067-1（2011年）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sulkowski, M. S. Management of the hematologic complications of hepatitis C therapy. Clin. Liver Dis. 9, 601–616, vi. https://doi.org/10.1016/j.cld.2005.07.007 (2005).Origa, R. β-Thalassemia. Genet. Med. 19, 609–619. https://doi.org/10.1038/gim.2016.173 (2017).Article

Sulkowski，M.S。丙型肝炎治疗血液学并发症的管理。临床。肝脏疾病。9601-616，vi。https://doi.org/10.1016/j.cld.2005.07.007（2005年）。Origa，R。β地中海贫血。基因。。https://doi.org/10.1038/gim.2016.173（2017年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Peng, W. et al. Prognostic value of the platelet to lymphocyte ratio change in liver cancer. J. Surg. Res. 194, 464–470. https://doi.org/10.1016/j.jss.2014.12.021 (2015).Article

Peng，W。等人。血小板与淋巴细胞比率变化在肝癌中的预后价值。J、 外科学第194464-470号决议。https://doi.org/10.1016/j.jss.2014.12.021（2015年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Meng, X. et al. The platelet-to-lymphocyte ratio, superior to the neutrophil-to-lymphocyte ratio, correlates with hepatitis C virus infection. Int. J. Infect. Dis. 45, 72–77. https://doi.org/10.1016/j.ijid.2016.02.025 (2016).Article

孟，X。等人。血小板与淋巴细胞的比率优于中性粒细胞与淋巴细胞的比率，与丙型肝炎病毒感染相关。Int.J.感染。Dis。45，72-77。https://doi.org/10.1016/j.ijid.2016.02.025（2016年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Sharma, A., Easow Mathew, M. & Puri, L. Splenectomy for people with thalassaemia major or intermedia. Cochrane Database Syst. Rev. 9, Cd010517. https://doi.org/10.1002/14651858.CD010517.pub3 (2019).Talaat, A., Ismail, N. A., Habib, S. A. & Orban, H. A. A. Role of iron chelators, hydroxyurea, and splenectomy on serum total antioxidant capacity in β-thalassemia.

Sharma，A.，Easow Mathew，M。＆Puri，L。脾切除术治疗重度或中度地中海贫血患者。Cochrane数据库系统。第9版，Cd010517。https://doi.org/10.1002/14651858.CD010517.pub3（2019年）。Talaat，A.，Ismail，N.A.，Habib，S.A。和Orban，H.A.A。铁螯合剂，羟基脲和脾切除术对β地中海贫血血清总抗氧化能力的作用。

Open Access Macedonian J. Med. Sci. (2020).Crary, S. E. & Buchanan, G. R. Vascular complications after splenectomy for hematologic disorders. Blood 114, 2861–2868. https://doi.org/10.1182/blood-2009-04-210112 (2009).Article .

开放获取马其顿医学科学杂志。（2020年）。Crary，S.E。＆Buchanan，G.R。脾切除术后血液学疾病的血管并发症。血液1142861-2868。https://doi.org/10.1182/blood-2009-04-210112。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Aggeli, C. et al. Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major. Int. J. Cardiol. 105, 80–84 (2005).Article

Aggeli，C.等。输血依赖型重型β地中海贫血患者的内皮功能障碍和炎症过程。国际心脏病杂志。。文章

PubMed

PubMed

Google Scholar

谷歌学者

Breuer, W. et al. Non-transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients. Am. J. Hematol. 87, 55–61. https://doi.org/10.1002/ajh.22203 (2012).Article

地中海贫血中非转铁蛋白结合铁：儿童和老年患者氧化还原活性形式的差异检测。美国血液学杂志。87，55-61。https://doi.org/10.1002/ajh.22203。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ajith, T. A. & Jayakumar, T. G. Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases. World J. Cardiol. 6, 1091–1099. https://doi.org/10.4330/wjc.v6.i10.1091 (2014).Article

。世界J.Cardiol。61091-1099年。https://doi.org/10.4330/wjc.v6.i10.1091（2014年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Incalza, M. A. et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul. Pharmacol. 100, 1–19. https://doi.org/10.1016/j.vph.2017.05.005 (2018).Article

Incalza，M.A.等人。与心血管和代谢疾病相关的内皮功能障碍中的氧化应激和活性氧。血管。药理学。100，1-19。https://doi.org/10.1016/j.vph.2017.05.005（2018年）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kedar, P. S., Gupta, V., Warang, P., Chiddarwar, A. & Madkaikar, M. Novel mutation (R192C) in CYB5R3 gene causing NADH-cytochrome b5 reductase deficiency in eight Indian patients associated with autosomal recessive congenital methemoglobinemia type-I. Hematology 23, 567–573. https://doi.org/10.1080/10245332.2018.1444920 (2018).Article .

。https://doi.org/10.1080/10245332.2018.1444920（2018年）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Haghpanah, S. et al. The effect of vitamin E and N-acetyl cysteine on oxidative status and hemoglobin level in transfusion-dependent thalassemia patients: A systematic review and meta-analysis. Iran. J. Blood Cancer (2023).Download referencesAcknowledgementsWe express our sincere gratitude to Prof Dr Nadia Aly Sadek for her invaluable guidance, and support throughout the process of writing and revising our paper.FundingThe authors declare that no external funding was received to support this research.

Haghpanah，S.等人。维生素E和N-乙酰半胱氨酸对输血依赖性地中海贫血患者氧化状态和血红蛋白水平的影响：系统综述和荟萃分析。伊朗。J、 血癌（2023）。下载参考文献致谢我们衷心感谢Nadia Aly Sadek博士在撰写和修改论文的整个过程中提供的宝贵指导和支持。资助作者声明没有收到任何外部资金来支持这项研究。

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).Author informationAuthors and AffiliationsDepartment of Basic Science, Pharos University in Alexandria, Canal El Mahmoudia Street, Beside Green Plaza Complex, Alexandria, EgyptMaha Abubakr Feissal RabieRadiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, EgyptSanaa A.

科学、技术与创新基金管理局（STDF）与埃及知识银行（EKB）合作提供开放获取资金。作者信息作者和附属机构亚历山大法罗斯大学基础科学系，Canal El Mahmoudia Street，Green Plaza Complex，Alexandria，EgyptMaha Abubakr Feissal Rabieraradiation Sciences Department，医学研究所，Alexandria University，Alexandria，EgyptSanaa A。

El BenhawyDepartment of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, EgyptInas M. MasoudDepartment of Applied Medical Chemistry, Medical Research Institute, Alexandria University, Alexandria, EgyptAmal R. R. ArabDepartment of Clinical Haematology, Medical Research Institute, Alexandria University, Alexandria, EgyptSally A.

El BenhawyDepartment of Pharos University in Alexandria，Alexandria，EgyptInas M.MasoudDepartment of Applied Medical Chemistry，Medical Research Institute，Alexandria University，Alexandria，EgyptAmal R.ArabDepartment of Clinical Haemotology，医学研究所，Alexandria University，Alexandria，EgyptSally A。

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PubMed Google ScholarContributionsMaha Abubakr Feissal Rabie: contributed to the research proposal idea and design, writing the manuscript, participated in the laboratory practical part of the research, contributed to data analysis, the interpretation of the results and manuscript writing, editing & revising.

PubMed谷歌学术贡献：为研究提案的想法和设计做出了贡献，撰写了手稿，参与了研究的实验室实践部分，为数据分析，结果解释以及手稿的撰写，编辑和修订做出了贡献。

Snaa A. El Benhawy: Contributed to data entry & manuscript preparation. Inas M. Masoud: Participated in the laboratory biochemical practical part of the research, contributed to data entry & analysis through SPSS, interpretation of the results and manuscript preparation and editing. Amal R.R. Arab: Contributed to data collection and manuscript revising.

Snaa A.El Benhawy：为数据输入和手稿准备做出了贡献。Inas M.Masoud：参与了研究的实验室生化实践部分，通过SPSS进行数据输入和分析，解释结果以及稿件的准备和编辑。Amal R.R.Arab：为数据收集和稿件修订做出了贡献。

Sally A.M. Saleh: Participated by doing data collection & manuscript revising.Corresponding authorCorrespondence to.

萨利·萨利赫（Sally A.M.Saleh）：参与数据收集和手稿修订。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleRabie, M.A.F., El Benhawy, S.A., Masoud, I.M. et al. Impact of met-haemoglobin and oxidative stress on endothelial function in patients with transfusion dependent β-thalassemia.

转载和许可本文引用本文Rabie，M.A.F.，El Benhawy，S.A.，Masoud，I.M.等人。met血红蛋白和氧化应激对输血依赖性β地中海贫血患者内皮功能的影响。

Sci Rep 14, 25328 (2024). https://doi.org/10.1038/s41598-024-74930-3Download citationReceived: 05 August 2024Accepted: 30 September 2024Published: 25 October 2024DOI: https://doi.org/10.1038/s41598-024-74930-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsTransfusion depended β-thalassemiaEASIXOxidative stressMet-HbMalondialdehyde

关键词融合依赖性β-地中海贫血氧化应激Met-HB丙二醛