利拉鲁肽对非酒精性脂肪性肝炎C57小鼠肝细胞凋亡及Bcl-2/Bax、Caspase-9表达的影响

Effects of Liraglutide on Hepatocyte Apoptosis and Bcl-2 / Bax, Caspase-9 Expression in non-alcoholic Steatohepatitis C57 mice

目的探讨GLP-1受体激动剂-利拉鲁肽对非酒精性脂肪性肝炎C57小鼠肝细胞凋亡及Bcl-2/Bax、Caspase-9表达的影响。方法将C57/BL6J小鼠随机分成对照组和高脂组,后者进一步分为生理盐水组、利拉鲁肽低剂量(0.3 mg/kg·d)和高剂量组(0.6mg/kg·d),每组8只,高脂饲料喂养8周建立非酒精性脂肪性肝炎模型后利拉鲁肽皮下注射4周。结果在高脂组中,与生理盐水组相比,利拉鲁肽组肝脏细胞炎症及脂质沉积明显减轻,肝细胞凋亡数量明显减少(P<0.05),血清谷胱甘肽、超氧化物歧化酶水平升高,Bax、Caspase-9 mRNA在肝脏表达明显下调(P<0.05),相反,血清丙二醛水平降低,Bcl-2 mRNA在肝脏的表达明显上调(P<0.05)。结论利拉鲁肽通过减轻氧化应激,调控Bcl-2/Bax、Caspase-9基因抑制非酒精性脂肪性肝炎细胞凋亡,缓解非酒精性脂肪肝进展。

Objective To investigate the effects of GLP-1 receptor agonist-liraglutide on hepatocyte apoptosis and Bcl-2/Bax,Caspase-9 expression in non-alcoholic steatohepatitis C57 mice.Methods C57/BL6J mice were randomly divided into a control group and a high-fat group,and the latter was further divided into a saline group,a low-dose liraglutide(0.3mg/kg·d),and a high-dose group(0.6mg/kg·d).There are 8 animals in each group.Non-alcoholic steatohepatitis model was established on high-fat diet for 8 weeks,followed by subcutaneous injection of liraglutide for 4 weeks.Results In the high-fat group,compared with the normal saline group,liver cell inflammation and lipid deposition were significantly reduced,the number of hepatocyte apoptosis was significantly reduced(P<0.05),serum glutathione and superoxide dismutase levels were increased,and Bax and Caspase-9 mRNA expression in the liver were significantly down-regulated ( P <0.05) in the liraglutide group. Conversely, serum malondialdehyde levels were reduced, and Bcl-2 mRNA expression was significantly up-regulated in the liver ( P <0.05). Conclusion Liraglutide reduces the oxidative stress, regulates Bcl-2/Bax, and Caspase-9 genes to inhibit the apoptosis of non-alcoholic steatohepatitis cells and relieve the progression of non-alcoholic steatohepatitis.