【摘要】 目的探讨凋亡相关基因在非酒精性脂肪性肝炎(NASH)发生发展中的作用机制,以及己酮可可碱(PTX)对非酒精性脂肪性肝炎(NASH)大鼠的抗凋亡作用。方法SD大鼠68只,标准饲料喂养1周后,随机分为8组:8周对照组(6只),8周模型组(10只),12周对照组(6只),12周模型组(10只),12周治疗组(10只),16周对照组(6只),16周模型组(10只),16周治疗组(10只)。用高脂饮食法建立大鼠非酒精性脂肪性肝炎模型,腹主动脉取血检测血浆谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,采用免疫组织化学的方法检测肝Bcl-2、Bax、Caspase-3蛋白的表达情况,应用RT-PCR检测Caspase-3 mRNA的转录情况。结果各模型组ALT、AST均高于对照组,且模型组的ALT、AST逐渐增高。免疫组织化学实验结果表明,与同周数的对照组相比,各周模型组Bcl-2、Bax、Caspase-3的表达均有显著性增加(P<0.05),与同周数的模型组相比,12周、16周PTX治疗组Bcl-2、Bax、Caspase-3的蛋白表达有显著的降低(P<0.05)。结论细胞凋亡是NASH的一个重要发病机制,己酮可可碱对NASH大鼠肝脏细胞凋亡有一定的抑制作用。更多还原

【Abstract】 Objective To investigate the mechanism of apoptosis related gene in the course of NASH and the effect of pentoxifylline on hepatic apoptosis of nonalcoholic steatohepatitis(NASH) in rats. Methods Rats fed a standard diet for one week were randomly divided into eight groups,8 weeks control group(n=6),8 weeks model group(n=10),12 weeks control group(n=6),12 weeks model group(n=10),the 12 weeks PTX treatment group(n=10),16 weeks control group(n=6),16 weeks model group(n=10),and the 16 weeks PTX treatment group(n=10),The three model groups and the two PTX treatment groups were fed a high-fat diet. Meanwhile the rats fed a standard diet served as control groups.After 8 weeks,the 8 weeks control group and the 8 weeks model group were sacrificed,while the 12 weeks PTX treatment group were given PTX [16 mg/(kg·d)] by intragastric administration. In the end of 12 weeks,the 12 weeks control group ,the 12 weeks model group and the 12 weeks PTX treatment group were sacrificed,while the 16 weeks PTX treatment group were given PTX [16mg/(kg·d)] by intragastric administration. Then all the rats of other three groups were sacrificed at the end of the 16th week. The serum activities of liver alanine aminot ransferase (ALT),aspartate aminotransferase (AST) of all rats were measured. The expression of bcl-2,bax and Caspase-3 proteins in livers were analyzed by immunohistochemistry,The expression of Caspase-3 mRNA was determined by RT-PCR. Results ALT and AST in three model groups increased significantly compared to the identical control groups. The expressions of bcl-2,bax and Caspase-3 proteins were increased significantly in the three model groups compared to the identical control groups respectively(P<0.05). The expressions of the 12 weeks and 16 weeks PTX treatment group decreased compared to the identical model groups respectively(P<0.05).Conclusion Apoptosis may play a role in the course of NASH. PTX may relieve hepatic apoptosis of nonalcoholic steatohepatitis(NASH) in rats.更多还原