溴隐停、罗格列酮和二甲双胍对改善多囊卵巢综合征(PCOS)大鼠胰岛素抵抗和下调促炎细胞因子及调血脂作用研究

Effects of bromocriptine,rosiglitazone and metformin on insulin resistance downregulating proinflammatory cytokines and metabolism of lipids in rats with polycystic ovary syndrome

目的:观察溴隐停、二甲双胍、罗格列酮分别对多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠胰岛素抵抗、促炎细胞因子和脂肪细胞因子及血脂的干预作用。方法:采用十一酸睾酮加绒促性素(human chorionic gonadotropin,HCG)建立PCOS大鼠模型,连续口服给予溴隐停、二甲双胍、罗格列酮6周,观察大鼠空腹血糖(fasting blood-glucose,FBG)、口服葡萄糖后2小时血糖(OGTT-2 h BG)、胰岛素(insulin,Ins)、血清TC、TG、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、TNF-α、睾酮(testosterone,T)、胰岛素样生长因子(insulin growthfactor-1,IGF-I)、高敏C反应蛋白(high sensitivityC-reactive protein,hs-CRP)、瘦素(leptin,L)、脂联素(adiponectin,A)、抵抗素(resistin,R)等的含量,并计算胰岛素敏感指数(insulinsensitivity index,ISI)的变化。结果:PCOS大鼠FBG、OGTT-2hBG、Ins、hs-CRP、TNF-α、leptin、resistin、IGF-I、TC、TG、LDL-C和T水平明显升高,而ISI和adiponectin、HDL-C含量显著降低,与空白对照组比较,差异有统计学意义(P<0.01);溴隐停、二甲双胍、罗格列酮均能不同程度地改善PCOS大鼠的上述病理改变(P<0.01～0.05)。结论:溴隐停、二甲双胍、罗格列酮均能不同程度地改善PCOS大鼠胰岛素抵抗(IR)、高胰岛素血症、高雄激素血症和血糖、血脂代谢异常,以及下调促炎细胞因子和脂肪细胞因子。

AIM：To investigate effects of bromocriptine,rosiglitazone and metformin on insulin resistance（IR）,proinflammatory cytokines, adipocytokines,blood glucose and lipid components in rats with polycystic ovary syndrome （PCOS）.METHODS：The PCOS rats were molded by testosterone undecanoate and human chorionic gonadotropin（HCG）,afterwards the rats were randomly divided into 4 groups：PCOS mold,bromocriptine,rosiglitazone and metformin;then all drugs were adiministered respectively by intragastric administration （i.g.） qd for 6 weeks.At the end of the experiment, the contents of fasting blood-glucose （FBG）,2-hours blood glucose after oral glucose tolerance test（OGTT-2 h BG）,insulin,total cholesterol（TC）,triglyceride（TG）,low-density lipoprotein cholesterol（LDL-C）,high-density lipoprotein cholesterol（HDL-C）,tumor necrosis factor（TNF-α）,testosterone（T）,insulin growth factor-1（IGF-1）,high sensitivity C-reactive protein（hs-CRP）,leptin（L）,adiponectin （A）,resistin（R） were determined,and the changes of insulin sensitivity index（ISI） was counted.RESULTS：Compared with the normal group,concentrations of FBG,OGTT-2 h BG, Ins,hs-CRP,TNF-α,leptin,resistin,IGF-I, TC,TG,LDL-C and T were increased obviously （P〈0.01）,but ISI,adiponectin and HDL-C were decreased significantly（P〈0.01） in PCOS rats.Bromocriptine,rosiglitazone and metformin could improve the pathologic changes in PCOS rats（P〈0.01 or P〈0.05）.CONCLUSION： Bromocriptine,rosiglitazone and metformin can improve IR,hyperinsulinemia,hyperandrogenemia reduce blood glucose,adjust components of blood lipid,downregulate proinflammatory cytokines and regulate adipocytokines in PCOS rats.