大黄酸上调糖尿病大鼠脂肪组织PPAR-γ及GluT-4表达并改善胰岛素敏感性

Rhein improves insulin sensitivity of diabetic rats by increasing the protein expression levels of PPAR-γ and GluT-4 in adipose tissue

目的探讨大黄酸改善糖尿病大鼠脂肪组织胰岛素敏感性及降血糖的作用机制。方法雄性Wistar大鼠随机分为对照组(NC,n=15)及糖尿病造模组(DM,n=40),DM组成模后随机分为糖尿病模型组(DM-C,n=15)和糖尿病大黄酸治疗组(DM-T,n=15)。DM-T组予大黄酸100mg·kg-1·d-1灌胃11周。实验末检测各组大鼠FBG、FIns、TG、TC、胰岛素敏感指数(ISI)、过氧化物酶体增殖物激活受体γ(PPAR-γ)及葡萄糖转运蛋白4(GluT-4)在脂肪组织的表达水平。结果17周末DM-C组较NC组FBG、TG明显升高,ISI明显降低,脂肪组织PPAR-γ及GluT-4蛋白表达明显降低;DM-T组较DM-C组FBG明显降低;ISI明显升高;脂肪组织PPAR-γ蛋白表达明显升高,积分光密度有统计学差异;GluT-4蛋白表达明显升高,积分密度(ID)有统计学差异。结论大黄酸可上调糖尿病大鼠脂肪组织PPAR-γ及GluT-4蛋白表达,降血糖并改善胰岛素敏感性。

Objective To investigate the mechanism for rhein to improve the insulin sensitivity in diabetes mellitus. Methods Male Wistar rats were randomly divided into normal control group （NC, n=15） and diabetic group （DM, n=40） induced by STZ and high-fat diet. Diabetic rats were randomly divided into diabetic control group （DM-C, n = 15） and diabetic group treated with rhein （DM T, n = 15）. Then DM-T group was given intragastric administration with rbein at the dose of 100 rng/ （kg^-1 · d^-1 ） for 11 weeks. FBG, fasting serum insulin （Fins）, triglyeeride （TG）, total cholesterol （TC）, insulin sensitivity index （ISI） and other biochemical parameters in each group were measured. The protein expressions of PPAR-γ and GluT-4 were determined by immunohistoehemistry and Western blot. Results At the end of the 17th week, compared with NC group, DMC group showed higher FRG and TG, lower ISI, lower protein expressions of PPARy and GluT-4 in the adipose tissue. Compared with DM-C group, DM-T group showed lower FBG E（15. 73±3. 08 vs 22. 57±3.23） mmol/1, P〈0. 01], higher ISI （-4.97±0. 29 vs -5.46±0. 61, P〈0. 05）. Integrated optical density （IOD） showed higher protein expression of PPAR-7 of DM-T group in adipose tissue as compared with DM-C group [13613.35 （7293. 85 ~17198.73） vs 4750.70 （3346.63～10390.63）, P〈0.01]. Integrated density （ID） showed higher protein expression of GluT 4 of DMT group in adipose tissue as compared with DM-C group [1.157 （0. 921～1. 953） vs 0. 828 （0. 621 ～1.010）, P〈0. 01]. Conclusions Rhein increases the protein expressions of PPAR-γ and GluT-4 in adipose tissue, decreases FBG and improves insulin sensitivity of diabetic rats.