阿司匹林增加高脂喂养Wistar大鼠胰岛素敏感性和Mfn2mRNA的表达

Aspirin Improves Insulin Sensitivity and Mfn2mRNA Expression in High-fat Treated Wistar Rats

关键词:  阿司匹林  胰岛素敏感性  线粒体  线粒体融合素基因2

Key words:  aspirin  insulin sensitivity  mitochondria  mitofusin-2 gene

摘要:

目的 研究阿司匹林对高脂喂养Wistar大鼠胰岛素敏感性和线粒体功能的影响。方法 24只Wistar大鼠，♂，分为对照组(NC)、高脂组(HF)和阿司匹林组(AF)(n=8)，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谷草转氨酶(ALT)、谷丙转氨酶(AST)、高密度脂蛋白(HDL-C)、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固定、包埋、切片和HE染色，观察肝脏组织学变化；取肝脏组织，测定肝糖原含量；提取肝细胞线粒体并分离线粒体超氧化物歧化酶，测定线粒体超氧化物歧化酶活性(SOD)，以及提取肝组织总RNA，应用RT-PCR测定肝脏组织Mfn2 mRNA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(P<0.05)，GIR和SOD显著降低(P<0.05)，肝脏组织Mfn2 mRNA表达显著降低，肝细胞体积增大，胞质中有脂滴空泡；AF组大鼠上述各指标差异无统计学意义，显微结构无显著变化。结论 阿司匹林可以改善高脂诱导的胰岛素抵抗及抑制脂肪肝的形成，这一作用可能是部分通过促进肝细胞Mfn2表达、改善线粒体功能实现的。

Abstract:

OBJECTIVE To investigate the effects of aspirin on insulin sensitivity and Mfn2 mRNA expression in rats fed with high-fat diet. METHODS Twenty-four male rats were randomly divided into normal control diet group (NC, n=8), high-fat diet group (HF, n=8) and aspirin group (AF, n=8) according to random digits table. After treatment with different diets for 8 weeks, insulin sensitivity was evaluated by measuring the glucose infusion rate (GIR) using a hyperinsulinemic euglycemic clamp. The levels of serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglycerides(TG), fasting blood sugar(FBS) and insulin(FINS) were measured respectively. The liver tissues of three groups were fixed, sliced, stained and observed with light microscope. The liver glycogen was determined. Superoxide dismutase (SOD) in liver mitochondria was extrated and measured. Mfn2 mRNA in hepatic tissue was detected by reverse transcription PCR. RESULTS Compared with the NC group, the liver index and the levels of serum TG, FBS, ALT, AST, and insulin in the HF group were statistically increased (P<0.05). The GIR, SOD, and expression of Mfn2 mRNA in the HF group were significantly decreased (P<0.05). However, there was no difference in above indicators between the NC group and the AF group. Pathological change of liver tissues by HE staining, normal hepatic plates were shown in NC and AF groups. In HF group, the liver cells of rats showed an increase in size, and included the storage of lipid droplets. CONCLUSION Aspirin can improve insulin sensitivity and inhibit hepatic steatosis by high-fat induced, may be partly attributable to promote expression of Mfn2 and improve mitochondrial function in liver of rats.