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慢性丙型肝炎患者血清可溶性Fas、Fas配体及肝内淋巴细胞Fas的临床意义

Clinical significance of serum soluble Fas, Fas ligand and fas in intrahepatic lymphocytes in chronic hepatitis C.

作者信息

Zaki Maysaa El Sayed, Auf Fatma Abbas, Ghawalby Nabieh Anwar El, Saddal Nirmeen Mohamed El

机构信息

Clinical Pathology Department, Mansoura University, Mansoura, Egypt.

出版信息

Immunol Invest. 2008;37(2):163-70. doi: 10.1080/08820130801897352.

Abstract

Hepatitis C Virus (HCV) is a major etiological agent of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Fas-mediated apoptosis is the major cause of hepatocyte damage during liver disease. The present work was performed to study the fas system (Fas-FasL and soluble Fas) in chronic hepatitis C infection. Also, to correlate the degree of liver cell damage with the Fas system. The study was carried out on 45 patients positive for HCV RNA by nested RT-PCR in addition to 13 HCV negative control subjects. Wedge liver biopsies samples were obtained from patients and controls during abdominal operations for determination of cellular expression of Fas and Fas-L on hepatocytes and infiltrating lymphocytes respectively by flow cytometry. Histological activity index (HAI) was determined in chronic HCV patients. Also blood samples were taken from patients and controls for determination of sFas. There was statistically insignificant difference in Fas expression in hepatocytes of patients (P = 0.34) in comparison to control. Meanwhile, there was a statistically significant decrease in FasL expression in patients compared to control (P< 0.001) and statistically significant increase in soluble Fas in patients compared to control (P < 0.001). The HAI of liver fibrosis for all patients were within mild score with mean +/- SD 4 +/- 0.5. From this study, we could conclude that Fas system is one of the important pathways regulating the response to HCV infection. Increased serum sFas in HCV patients is accompanied by down-regulation of Fas/Fas-L expression resulting in inhibition of apoptosis in liver cells as a process for elimination of virus infected cells and this may ultimately leads to chronicity of the disease.

摘要

丙型肝炎病毒(HCV)是慢性肝炎、肝硬化和肝细胞癌的主要病因。Fas介导的细胞凋亡是肝病期间肝细胞损伤的主要原因。本研究旨在探讨慢性丙型肝炎感染中的Fas系统(Fas - FasL和可溶性Fas)。此外,还将肝细胞损伤程度与Fas系统相关联。除13名HCV阴性对照受试者外,对45例经巢式RT - PCR检测HCV RNA阳性的患者进行了研究。在腹部手术期间从患者和对照中获取楔形肝活检样本,通过流式细胞术分别测定肝细胞和浸润淋巴细胞上Fas和Fas - L的细胞表达。测定慢性HCV患者的组织学活动指数(HAI)。还从患者和对照中采集血样以测定sFas。与对照相比,患者肝细胞中Fas表达的差异无统计学意义(P = 0.34)。同时,与对照相比,患者中FasL表达有统计学意义的降低(P < 0.001),与对照相比,患者中可溶性Fas有统计学意义的增加(P < 0.001)。所有患者的肝纤维化HAI均在轻度范围内,平均±标准差为4±0.5。从本研究中,我们可以得出结论,Fas系统是调节对HCV感染反应的重要途径之一。HCV患者血清sFas升高伴随着Fas/Fas - L表达下调,导致肝细胞凋亡受到抑制,而细胞凋亡是清除病毒感染细胞的过程,这最终可能导致疾病的慢性化。

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