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重型β地中海贫血患者血清中细胞死亡循环生物标志物M30和M65水平升高。

Elevated serum levels of cell death circulating biomarkers, M30 and M65, in patients with β-thalassemia major.

作者信息

Esmaeil Nafiseh, Moayedi Behjat, Gharagozloo Marjan, Maracy Mohamad Reza

机构信息

Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Hemoglobin. 2013;37(4):404-10. doi: 10.3109/03630269.2013.790828. Epub 2013 Apr 19.

DOI:10.3109/03630269.2013.790828
PMID:23600495
Abstract

Deposition of iron in visceral organs, mainly in the liver, causes tissue damage in β-thalassemia major (β-TM) patients. Keratin 18 (K18) represents one of the major caspase substrates during apoptosis of hepatocytes. To better characterize the hepatic apoptosis and/or necrosis in β-thal patients, the circulating levels of M65 (soluble intact K18) and M30 (the caspases-generated K18 fragment) were measured in 40 β-TM patients and compared with 40 healthy controls. The ratio of M30/M65 (caspase-cleaved to total K18) was also determined in thalassemic and normal subjects. Results of the ELISA assays revealed that the serum levels of hepatocyte death markers, M65 and M30, were significantly increased in β-thal patients compared to healthy controls (p <0.0001). M30 serum levels were also positively correlated with the serum levels of liver transaminases including aspartate aminotransferase (AST) (r = 0.337, p = 0.047) and alanine aminotransferase (ALT) (r =0.391, p = 0.02).

摘要

铁在主要是肝脏的内脏器官中沉积,会导致重型β地中海贫血(β-TM)患者出现组织损伤。角蛋白18(K18)是肝细胞凋亡过程中的主要半胱天冬酶底物之一。为了更好地表征β地中海贫血患者肝脏的凋亡和/或坏死情况,我们检测了40例β-TM患者循环中M65(可溶性完整K18)和M30(半胱天冬酶产生的K18片段)的水平,并与40名健康对照者进行比较。还测定了地中海贫血患者和正常受试者中M30/M65(半胱天冬酶切割的K18与总K18的比例)。酶联免疫吸附测定(ELISA)结果显示,与健康对照者相比,β地中海贫血患者肝细胞死亡标志物M65和M30的血清水平显著升高(p<0.0001)。M30血清水平也与包括天冬氨酸转氨酶(AST)(r=0.337,p=0.047)和丙氨酸转氨酶(ALT)(r=0.391,p=0.02)在内的肝转氨酶血清水平呈正相关。

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