益肾I方对多囊卵巢综合征—代谢综合征大鼠拮抗胰岛素抵抗抑制氧化应激及调血脂作用

目的观察益肾I方对多囊卵巢综合征-代谢综合征(PCOS-MetS)大鼠胰岛素抵抗(IR)、血脂异常及氧化应激-自由基损伤的作用。方法采用十一酸睾酮加绒毛膜促性腺激素(HCG)建立PCOS-MetS大鼠模型,连续口服给予二甲双胍或不同剂量的益肾I方4周,观察大鼠体质量、血清肿瘤坏死因子-α(TNF-α)、睾酮(T)、丙二醛(MDA)、一氧化氮(NO)、胆固醇(TC)、甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)和口服葡萄糖后2h血糖(OGTT-2hBG)和胰岛素含量以及超氧化物歧化酶(SOD)和诱导型一氧化氮合酶(iNOS)-一氧化氮合酶(NOS)活性,并计算胰岛素敏感指数(ISI)的变化。结果PCOS-MetS大鼠体质量明显增加,与空白对照组比较,差异有统计学意义(P<0.01);血清TNF-α、T、MDA、NO、TG、TC、LDL-C、FBG、OGTT-2hBG和胰岛素水平以及iNOS-NOS活性,均明显升高,而HDL-C含量、SOD活性和ISI则显著降低,与空白对照组比较,差异有统计学意义(P<0.01);二甲双胍和益肾I方高和中2个剂量均能不同程度地改善PCOS-MetS大鼠体质量增加、高雄激素血症、高血糖血症、高脂血症、高胰岛素血症和IR等病理生理改变(P<0.01或P<0.05),以及增强抗氧化酶SOD活性,抑制NOS和iNOS活性,降低MDA和NO水平(P<0.01或P<0.05)。结论益肾I方能改善PCOS-MetS大鼠胰岛素敏感性,对抗高雄激素血症和脂质代谢异常以及氧化应激-自由基损伤,并提高抗氧化能力。

Effects of Yishenyifang against insulin resistance, dyslipidemia and free radical injury in rats with polycystic ovary syndrome and metabolic syndrome

Objective To investigate the effect of Yishenyifang （called YSYF for short in the following） against insulin resistance, blood glucose-lipid abnormalities and free radical injury in rats with polycystic ovary syndrome （PCOS） and metabolic syndrome （MetS）. Methods Model of PCOS-MetS was induced by testosterone undecanoate and HCG subcutaneously （sc） injected in different period, as well as the blank control group sc injection in rats; afterwards, 70 rats were randomly divided into 5 groups according to body weight ： there were 14 rats in model group of PCOS-MetS, 42 in experimental drug groups which were given by YSYF 25 g/kg, 12.5 g/kg and 6.25 g/kg, 14 in positive control group by the administration of mefformin （0.25 g/kg）, as well as 14 in the blank control group; then all drugs or solvent were adiministered respectively by intragastric administration （ig）, qd for 6 weeks. At the end of the experiment, the body weight was measured, the contents of fasting blood-glucose （FBG）, 2-hours blood glucose after oral glucose tolerance test （OGTT-2hBG）, insulin （Ins）, total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, triglyceride （TG）, tumor necrosis factor （TNF） -α, testosterone （T）, malondialdehyde （MDA）, nitric oxide （NO） were determined, and activities of inducible nitric oxide synthase （iNOS）, nitric oxide synthase （NOS） and superoxide dismutase activity （SOD） were tested, and the change of insulin sensitivity index （ISI） was counted. Results Compared with the normal group, body weight, FBG, OGTT-2hBG, Ins, TC, TG, LDL-C, TNF-α, T, MDA, NO and iNOS increased significantly （P〈0.01）, but ISI, HDL-C and SOD decreased obviously （P〈0.01）. All groups of metformin and YSYF high and middle dosages could reduce the levels of FBG, OGTT-2hBG, Ins, TC, LDL-C, TG, TNF-α, T, MDA, NO and activities of iNOS and NOS, and improve activity of SOD, increase concentration of HDL-C and enhance ISI, etc in PCOS-MetS rats （P〈0.01 or P〈0.05）. Conclusion Yishenyifang and metformin can significantly improve the insulin senfitivity and ameliorate blood glucose and lipid metabolism and antagonize pathologic changes of dyslipidemia, hyperinsulinemia, hyperandrogenemia and free radical injury in PCOS- MetS rats.