利拉鲁肽对NAFLD大鼠的保护作用及其与ERp46蛋白表达的相关性研究

Study on the protective effect of liraglutide on NAFLD rats and its correlation with ERp46 protein expression

目的研究利拉鲁肽对非酒精性脂肪性肝病(NAFLD)大鼠的保护作用及其与ERp46蛋白表达的相关性。方法取24只雄性SD大鼠随机分为对照组(8只,正常饲养)和实验组(16只,高脂饮食);喂养3个月后,将实验组随机分为A组(给予生理盐水)和B组(给予利拉鲁肽100 g/kg)各8只。各组均行苏木精-伊红(HE)染色处理,并进行正常葡萄糖-高胰岛素钳夹试验,采用TUNEL法检测肝细胞凋亡情况;采用Western印迹法对各组大鼠肝脏组织中ERp46蛋白的表达情况进行检测。结果 A组葡萄糖输注率较对照组明显下降(P <0. 05);B组大鼠葡萄糖输注率较A组显著升高,但较对照组明显下降(P <0. 05)。A组肝细胞凋亡率较对照组明显升高(P <0. 05);B组大鼠肝细胞凋亡率较A组明显降低,但较对照组仍明显升高(P <0. 05)。A组大鼠肝脏组织中ERp46蛋白表达水平较对照组显著下降(P <0. 05);B组大鼠肝脏组织中ERp46蛋白表达水平较A组明显上调(P <0. 05),而与对照组表达水平的比较,无显著差异(P> 0. 05)。结论利拉鲁肽对NAFLD大鼠肝脏组织具有一定的保护作用,其可能通过提高ERp46的表达水平而发挥减轻NAFLD大鼠胰岛素抵抗和肝脏脂肪变性、减少肝细胞凋亡的作用。

Objective To study the protective effect of liraglutide on non-alcoholic fatty liver disease( NAFLD) rats and its correlation with the expression of ERp46 protein. Methods Twenty-four male SD rats were randomly divided into control group( 8 rats,normal feeding)and experimental group( 16 rats,high-fat diet). After feeding for three months,the experimental group was randomly divided into group A( normal saline) and group B( liraglutide 100 g/kg) with 8 rats in each group. Hematoxylin-eosin( HE) staining was performed in all groups,and normal glucose-hyperinsulinemia clamp test was carried out. Apoptosis of hepatocytes was detected by TUNEL method,and ERp46 protein expression was detected by Western blotting. Results The glucose infusion rate in group A was significantly lower than that in control group( P <0. 05). The glucose infusion rate in group B was significantly higher than that in group A,but significantly lower than that in control group( P <0. 05). The apoptotic rate of hepatocytes in group A was significantly higher than that in control group( P < 0. 05). The apoptotic rate of hepatocytes in group B was significantly lower than that in group A,but still significantly higher than that in control group( P < 0. 05). The expression level of ERp46 in liver tissue of group A was significantly lower than that of control group( P < 0. 05). The expression level of ERp46 in liver tissue of group B was significantly higher than that of group A( P < 0. 05),but there was no significant difference between group A and control group( P > 0. 05). Conclusion Liraglutide has a protective effect on liver tissue of NAFLD rats. It may play a role in reducing insulin resistance,hepatic steatosis and hepatocyte apoptosis by increasing the expression of ERp46 in NAFLD rats.