大鼠肝脏癌前病变肝细胞凋亡及Fas/FasL的表达

目的探讨肝脏癌前病变过程中肝细胞凋亡的变化及Fas和FasL的表达,以期为肝脏疾病防治提供实验依据。方法将大鼠随机分为对照组和模型组,模型组采用腹腔注射二乙基亚硝胺(DEN)制备大鼠肝脏癌前病变模型,生化检查血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(γ-GT)、α-L-岩藻糖苷酶(AFU)、甲胎蛋白(AFP)和癌胚抗原(CEA)。光镜下观察肝脏组织病理学改变;使用DNA电泳法检测肝细胞的凋亡情况;应用免疫组织化学法检测Fas和FasL的表达与分布。结果对照组大鼠光镜下肝组织结构正常,模型组大鼠肝细胞肿胀,肝小叶内可见灶性坏死伴炎性细胞浸润,同时逐渐出现纤维组织增生及肝细胞再生。模型组1～8周和9～12周大鼠血清ALT、AST、γ-GT和AFU活性均高于对照组,差别有统计学意义(P<0.01);模型组9～12周大鼠血清ALT、AST、γ-GT和AFU活性高于1～8周,差别有统计学意义(P<0.05),2组AFP和CEA均正常。对照组无细胞凋亡,模型组大鼠肝脏细胞呈明显的DNA梯状条带。对照组大鼠肝组织中未见Fas和FasL表达,模型组Fas和FasL主要表达在肝脏细胞胞浆。结论大鼠肝脏癌前病变时,肝细胞凋亡增加可能与凋亡相关基因Fas和FasL表达增加有关。肝脏癌前病变大鼠肝细胞凋亡增加,可能是肝损伤加重的原因。

Apoptosis and Fas/FasL expression of hepatic cells in rat precancerous lesion of liver

Objective To investigate the apoptosis and Fas/FasL expression of liver cells during liver precancerous lesion,and to provide experimental basis for treatment and prevention of liver disease.Methods Rats were randomly divided into control group and experiment group.The rat liver precancerous lesion models were established by injecting diethylnitrosamine (DEN) in intraperitoneal.Alanine amiotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptadase(γ-GT),α-L-fucosidase(AFU),alpha-fetoprotein(AFP) and carcinoembryonic antigen(CEA) content in serum,were measured by biochemical technology.Liver pathological characteristics were examined by microscope.The apoptosis of liver cells was detected by DNA agarose electrophoresis.The localization and expression of Fas and FasL were identified by immunohistoehemistry. Results The liver tissue was normal in the control group.The liver cell appeared engorge;Focal necrosis and inflammatory cell infiltration were discovered in hepatic lobules;Fibroplasia and regeneration gradually occurrenced in model group.Compared with control group,the ALT,AST,γ-GT and AFU content in serum in model group 1-8 weeks and 9-12 weeks were increased(P<0.01);The ALT,AST,γ-GT and AFU content in serum of model group during 9-12 weeks were significantly higher than 1-8 weeks(P<0.05),and AFP and CEA content in serum remained unchanged in model group.The hepatocyte apoptosis was not found in the control group.The obvious DNA ladder was observed in liver cell in the model group.The Fas and FasL expression were not found in the control group.Fas and FasL expressed mainly in the liver cell cytoplasm in the model group.Conclusion The increase of liver cell apoptosis may be closely related with the increase of Fas/FasL expression in the rat liver precancerous lesion.The increase of the hepatocyte apoptosis may be reasons of liver damage aggravation in rat liver precancerous lesion.