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出 处:《山西医科大学学报》2011年第7期529-531,611,共4页Journal of Shanxi Medical University
基 金:山西省自然科学基金资助项目(2008011073-1)
摘 要:目的通过观察非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)发生发展过程中LPS对肝细胞凋亡的影响,初步探讨LPS与NASH发病机制的内在联系。方法 30只雄性Wistar大鼠随机分为LPS组、NASH组、LPS+NASH组。LPS组饲以普通饮食,其余两组饲以高糖高脂饮食。LPS组和LPS+NASH组经皮下隔日注射LPS 0.5 mg/kg。于实验第9周末处死动物,制备肝组织切片,观察肝组织病理改变、计数凋亡细胞;测定血浆内毒素水平和丙氨酸转氨酶(alanine amino trnsferase,ALT)活性、肿瘤坏死因子-α(TNF-α)水平。结果 LPS+NASH组动物肝组织切片凋亡细胞数、血浆ALT、TNF-α水平与NASH组比较均显著增高(P<0.05)。结论 LPS可明显加重高糖高脂所致的NASH。LPS可能通过上调TNF-α水平、诱导肝细胞凋亡,从而促进NASH的发展过程。Objective To investigate the effect of lipopolysaccharide(LPS) on hepatocyte apoptosis in the development of nonalcoholic steatohepatitis(NASH),and to explore the role of LPS in the pathogenesis of NASH. Methods Thirty male Wistar rats were assigned randomly into 3 groups:LPS group,NASH group and LPS+NASH group.The rats were given normal diet in LPS group,high-sucrose and high-fat diet in NASH group and LPS+NASH group.And the rats in LPS group and LPS+NASH group were additionally injected with LPS 0.5mg/kg every other day.The blood from various rats was collected sterilely for determining plasma ALT,TNF-α at the end of week 9.HE and TUNEL were used to observe the hepatic pathological changes and hepatocyte apoptosis respectively. Results Levels of ALT and TNF-α in plasma were significantly higher in LPS+NASH group than in NASH group.Histology with hematoxylin and eosin staining showed that steatosis of hepatocyte was severe obviously with larger lipid droplet in LPS+NASH group than in NASH group.And histology with TUNEL staining showed that the hepatocyte apoptosis was significantly higher in LPS+NASH group than in LPS group. Conclusion LPS could induce the hepatocyte apoptosis by up-regulating TNF-α production,and thus promote the development of NASH.
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