Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis
Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis
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DOI：
10.1016/s0016-5085(03)00907-7
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发表时间：
2003-08-01
期刊：
影响因子：
29.4
通讯作者：
Gores, GJ
中科院分区：
文献类型：
--
作者：
Feldstein, AE;Canbay, A;Gores, GJ
背景与目的：非酒精性脂肪性肝炎（NASH）的发病机制仍知之甚少。尽管细胞凋亡是肝脏损伤的常见机制，但NASH中细胞凋亡的程度及其临床意义尚未得到研究。因此，本研究的目的是量化NASH中的肝细胞凋亡，将其与疾病严重程度相关联，并确定诱导凋亡的可能机制。
方法：采用TUNEL法以及针对活化的半胱天冬酶3和7的免疫组织化学方法，对NASH、单纯性脂肪变性、酒精性肝炎以及无肝病的对照组的肝细胞凋亡进行评估。还根据炎症和纤维化的程度对肝脏标本进行分级。
结果：与单纯性脂肪变性和对照组相比，NASH患者肝活检标本中的TUNEL阳性细胞显著增加。出乎意料的是，与酒精性肝炎相比，NASH中的TUNEL阳性细胞也更多。免疫组织化学显示NASH标本中存在活化的半胱天冬酶3和7，证实了该疾病中存在细胞凋亡。分别观察到肝细胞凋亡与肝纤维化和炎症活动之间呈正相关。与对照组相比，NASH患者肝脏标本中的肝细胞强烈表达Fas受体。
结论：NASH患者的肝细胞凋亡显著增加，并与疾病严重程度相关，这表明抗凋亡治疗可能对该综合征有用。
Background & Aims: The pathogenesis of nonalcoholic steatohepatitis (NASH) remains poorly understood. Although apoptosis is a common mechanism of liver injury, the extent and clinical significance of apoptosis in NASH has not been examined. Thus, the aims of this study were to quantify hepatocyte apoptosis in NASH, correlate it with disease severity, and identify possible mechanisms of apoptosis induction. Methods: Hepatocyte apoptosis was assessed in NASH, simple steatosis, alcoholic hepatitis, and controls without liver disease using the TUNEL assay and immunohistochemistry for activated caspases 3 and 7. Liver specimens were also graded according to the magnitude of inflammation and fibrosis. Results: TUNEL-positive cells were significantly increased in liver biopsy specimens from patients with NASH compared with simple steatosis and controls. Unexpectedly, TUNEL-positive cells were also greater in NASH vs. alcoholic hepatitis. Immunohistochemistry demonstrated active caspases 3 and 7 in NASH specimens, confirming the occurrence of apoptosis in this disease. A positive correlation was observed between hepatocyte apoptosis and hepatic fibrosis and inflammatory activity, respectively. The Fas receptor was strongly expressed in hepatocytes in liver specimens from NASH patients as compared with controls. Conclusions: Hepatocyte apoptosis is significantly increased in patients with NASH and correlates with disease severity, suggesting that antiapoptotic therapy may be useful in this syndrome.