论文部分内容阅读
目的研究二甲双胍对高脂喂养Wistar大鼠肝脏脂肪变性、胰岛素敏感性和线粒体功能的影响。方法24只雄性Wistar大鼠分为对照组(NC)、高脂组(HF)和二甲双胍组(MF),每组8只,喂养8周后,以高胰岛素-正常葡萄糖钳夹测定大鼠胰岛素敏感性,取空腹血清测定大鼠天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)、甘油三酯(TG)、空腹血糖(FBS),空腹胰岛素(FINS)的水平;将大鼠肝脏组织进行HE染色,观察肝脏组织学变化;取肝脏组织,测定肝糖原含量;提取、分离肝细胞线粒体超氧化物歧化酶,测定线粒体超氧化物歧化酶活性,以及提取肝组织总RNA,应用RT-PCR测定肝脏组织Mfn2mRNA的表达。结果与NC组大鼠比较,HF组大鼠肝脏指数、TG、FBS、ALT、AST、INS明显升高,MF组大鼠上述各指标差异无统计学意义(P>0.05),HF组大鼠GIR、SOD活性及肝脏组织Mfn2mRNA表达显著降低(P<0.05)。与NC组和HF组大鼠分别比较,MF组大鼠GIR(8.40±0.50,7.29±0.40 vs 12.92±8.33)、肝糖原含量(1.73±0.01,1.82±0.31 vs 12.92±8.33)、SOD活性(13.71±2.67,9.08±3.12 vs 16.72±4.80)显著增加(P<0.05)。NC和HF两组间,肝糖原含量差异无统计学意义(P>0.05)。肝组织HE染色,结果显示,HF组大鼠肝细胞体积增大,胞质中有脂滴空泡;MF组大鼠肝细胞显微结构无显著变化。结论二甲双胍可以改善高脂诱导的肝脏脂肪变性、增加胰岛素敏感性,这一作用可能是通过促进肝细胞线粒体融合基因2(Mfn2)表达、改善线粒体功能实现的。
Objective To investigate the effects of metformin on hepatic steatosis, insulin sensitivity and mitochondrial function in high fat diet Wistar rats. Methods Twenty-four male Wistar rats were divided into control group (NC), high fat group (HF) and metformin group (MF), with 8 rats in each group. After 8 weeks of feeding, insulin was measured by hyperinsulinemic-normal glucose clamp The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), fasting blood glucose (FBS) and fasting insulin (FINS) The liver tissues of rats were subjected to HE staining to observe the histological changes of the liver. The liver tissue was taken and the content of hepatic glycogen was determined. The activities of mitochondrial superoxide dismutase (SOD) in liver cells were extracted and separated, and the activities of total liver tissue RNA, the expression of Mfn2 mRNA in liver tissue was detected by RT-PCR. Results The liver index, TG, FBS, ALT, AST and INS in HF group were significantly increased compared with those in NC group. There was no significant difference in the above indexes between MF group and HF group (P> 0.05) GIR, SOD activity and liver tissue Mfn2mRNA expression was significantly lower (P <0.05). Compared with the NC group and the HF group, GIR (8.40 ± 0.50, 7.29 ± 0.40 vs 12.92 ± 8.33), hepatic glycogen content (1.73 ± 0.01, 1.82 ± 0.31 vs 12.92 ± 8.33), SOD activity (13.71 ± 2.67,9.08 ± 3.12 vs 16.72 ± 4.80) (P <0.05). There was no significant difference in hepatic glycogen between NC and HF (P> 0.05). Liver tissue HE staining, the results showed that the volume of liver cells in HF group increased, the lipid droplets in the cytoplasm vacuoles; MF group of rat liver cells showed no significant changes in microstructure. Conclusion Metformin can improve the fatty liver-induced hepatic steatosis and increase insulin sensitivity. This effect may be achieved through the promotion of mitochondrial function by promoting the expression of mitochondrial fusion 2 (Mfn2) in hepatocytes.