绞股蓝总皂苷对2型糖尿病大鼠游离脂肪酸代谢的影响及改善胰岛素抵抗相关机制研究

Effect of total saponins from Gynostemma pentaphyllum on free fatty acid metabolism of type 2 diabetes rats and its mechanisms of improving insulin resistance

目的探讨绞股蓝总皂苷(GPS)对2型糖尿病(T2DM)大鼠游离脂肪酸代谢的影响并初步探讨其改善胰岛素抵抗的作用机制。方法 80只大鼠腹腔注射40 mg·kg-1链脲佐菌素,并加高脂饲料喂养构建T2DM脂代谢紊乱模型,选取50只成模大鼠随机分为模型组(n=10)、二甲双胍组(n=10)、GPS低剂量组(n=10)、GPS中剂量组(n=10)和GPS高剂量组(n=10)。二甲双胍和不同GPS剂量干预4周后,测定空腹血糖(FPG)、糖化血红蛋白(Hb A1C)、游离脂肪酸(FFA)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、胰岛素(INS)、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)和定量胰岛素敏感性检测指数(QUIC-KI)。结果模型组与GPS低剂量组细胞凋亡指数(AI)较正常组显著升高(P<0.05);各治疗组AI较模型组显著降低(P<0.05);GPS高剂量组和二甲双胍组AI较中剂量组显著降低(P<0.05);GPS高剂量组AI和二甲双胍组AI差异无统计学意义(P>0.05)。模型组FPG、Hb A1C、FFA、TG、TC、LDL-C、INS和HOMA-IR均高于正常组水平,而HDL-C、QUICKI和HOMA-β均低于正常组,均差异有统计学意义(P<0.05)。经二甲双胍和GPS干预后,各模型组FPG、Hb A1C、FFA、TG、TC、LDL-C、INS和HOMA-IR较干预前均明显降低,而HDL-C、QUICKI和HOMA-β较干预前均明显升高(P<0.05)。相关性分析结果显示,HOMA-IR与FPG、Hb A1C、FFA、TG、TC和LDL-C呈明显的正相关,与HDL-C和体质量呈明显的负相关(P<0.05)。结论 GPS可明显改善T2DM中出现的胰岛素抵抗,其机制与绞股蓝总皂苷改善脂代谢紊乱和降血糖的作用有关。

Objective To investigate the effects of total saponins from Gynostemma pentaphyllum（ GPS） on free fatty acid metabolism of type 2 diabetes and its mechanisms of improving insulin resistance. Methods Eighty rats intraperitoneally injected 40 mg·kg-1streptozotocin and given high fat diet for building model of type 2 diabetic rats with lipid metabolism disorders. Fifty model rats were randomly divided into model group（ n = 10）,metformin group（ n = 10）,GPS low-dose group（ n = 10）,GPS moderate-dose group（ n = 10）,GPS highdose group（ n = 10）. After four weeks intervention with metformin and different doses of GPS,fasting blood glucose（ FPG）,glycosylated hemoglobin（ Hb Alc）,free fatty acid（ FFA）,triglyceride（ TG）,total cholesterol（ TC）,low-density lipoprotein cholest（ LDL-C）,high density lipoprotein cholest（ HDL-C）,insulin（ INS）,HOMA-IR,HOMA-β,QUICKI were measured. Results Compared with the normal group,apoptotic indexes（ AI） in the model group and low GPS dose group,were significantly higher（ P〈0. 05）. The AI of each treatment group were significantly reduce（ P〈0. 05）. The AI of GPS high-dose group and metformin group were significantly lower than the middle dose group（ P〈0. 05）. There was no significant difference of AI between the GPS high dose group and the metformin group（ P〈0. 05）.FPG,Hb A1 C,FFA,TG,TC,LDL-C,INS and HOMA-IR levels were higher than normal group,while HDL-C,QUICKI and HOMA-β in model group were lower than those in the normal group,showing statistically difference differences（ P〈0. 05）. After the intervention of metformin and GPS,FPG,Hb A1 C,FFA,TG,TC,LDL-C,INS and HOMA-IR in each model group were significantly decreased compared with those before intervention,while HDL-C,HOMA-β and QUICKI significantly increased（ P〈0. 05）. Correlation analysis showed that,HOMA-IR exhibited a significant positive correlation with FPG,Hb A1 C,FFA,TG,TC and LDL-C and a significant negative correlation with HDL-C and weight（ P〈0. 05）. Conclusion Total saponins from Gynostemma pentaphyllum can lower the occurrence rate of the insulin resistance of type 2 diabetes,which the mechanism is involving improving dyslipidemia and hypoglycemia.