BACKGROUND/AIMS:Apoptosis has been implicated in the pathogenesis of fulminant hepatic failure (FHF) potentially involving caspases. Thus far, apoptosis in FHF has mainly been studied in animal models while human data are sparse. METHODS:Caspases-3, -8 and -9 activities and Fas expression were analyzed in correlation to TdT-mediated dUTP nick end labelling (TUNEL) positive apoptotic cells in livers of patients with FHF (n=26), chronic liver disease (CLD) (n=60) and normal controls (NC) (n=10). RESULTS:Numbers of TUNEL-positive cells were higher in FHF than in CLD and NC (P<0.001) correlating to the intrahepatic activities of caspase-3. The highest caspase-3 activities were found in fulminant hepatitis B, significantly surpassing those in FHF of any other etiology. In fulminant hepatitis B, caspase-9 activity was also higher than in controls, while caspase-8 activation was not higher than in NC. Unlike caspase-3, caspases -8 and -9 activities were not correlated to the numbers of TUNEL positive cells. Fas expression was also the highest in FHF but did not differ between hepatitis B virus-FHF and other FHF. CONCLUSIONS:Our data indicate differential activation of intrahepatic caspases in FHF depending on the underlying etiology. Massive activation of caspases in fulminant hepatitis B confirms a pivotal role of apoptotic pathways in the pathogenesis of human fulminant hepatitis B.

译文

背景/目的:细胞凋亡与可能涉及胱天蛋白酶的暴发性肝衰竭(FHF)的发病机制有关。迄今为止,主要是在动物模型中研究了FHF中的细胞凋亡,而人类数据却很少。
方法:分析FHF(n = 26),慢性肝病(CLD)患者肝脏中Taspase-3,-8和-9的活性以及Fas表达与TdT介导的dUTP缺口末端标记(TUNEL)阳性凋亡细胞的相关性。 )(n = 60)和正常对照(NC)(n = 10)。
结果:与caspase-3的肝内活性相关,FHF中TUNEL阳性细胞数高于CLD和NC(P <0.001)。在暴发性乙型肝炎中发现最高的caspase-3活性,大大超过了其他任何病因的FHF中的caspase-3活性。在暴发性乙型肝炎中,caspase-9的活性也高于对照组,而caspase-8的激活并不高于NC。与胱天蛋白酶3不同,胱天蛋白酶-8和-9的活性与TUNEL阳性细胞的数量无关。 Fas表达在FHF中也最高,但在乙型肝炎病毒FHF和其他FHF之间没有差异。
结论:我们的数据表明FHF肝内胱天蛋白酶有不同的激活作用,这取决于潜在的病因。暴发性乙型肝炎中胱天蛋白酶的大量激活证实了凋亡途径在人类暴发性乙型肝炎发病机理中的关键作用。

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