二甲双胍联合芍药甘草汤对多囊卵巢综合征大鼠的影响

Effect of metformin and peony-glycyrrhiza decoction on polycystic ovary syndrome in rats

目的研究二甲双胍联合芍药甘草汤对多囊卵巢综合征(PCOS)模型大鼠的影响。方法采用连续灌胃来曲唑21 d造模,将50只SD大鼠随机分为正常组、模型组、二甲双胍组、芍药甘草汤组、联合用药组,每组10只。药物干预后观察各组大鼠动情周期和卵巢形态学变化;酶联免疫吸附试验(ELISA)测定大鼠血清睾酮(T)、雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)、血糖、胰岛素、总胆固醇(TC)、瘦素水平;乳酸试剂盒测定血清乳酸水平;实时荧光定量聚合酶链反应(RT-PCR)测定卵巢组织胰岛素受体、瘦素受体mRNA的表达。结果与正常组比较,模型组大鼠动情周期紊乱,卵巢组织结构发生病变;血清T、LH、血糖、胰岛素、TC、瘦素水平明显升高(P<0.05),而E2、FSH水平明显降低(P<0.05);卵巢胰岛素受体、瘦素受体mRNA表达明显降低(P<0.05);血清乳酸水平略升高,但差异无统计学意义(P>0.05)。与模型组比较,各治疗组大鼠动情周期恢复正常,卵巢组织结构改善;芍药甘草汤组血清T、LH、胰岛素水平明显降低(P<0.05),E2水平明显升高(P<0.05),而其他糖脂代谢指标如血糖、TC、瘦素水平差异无统计学意义(P>0.05);二甲双胍组血清胰岛素、血糖、TC、瘦素水平明显降低(P<0.05),卵巢胰岛素受体、瘦素受体mRNA表达明显升高(P<0.05),而性激素如T、LH与E2水平差异无统计学意义(P>0.05);联合用药组大鼠上述性激素水平、糖脂代谢指标均有明显改善。结论二甲双胍联合芍药甘草汤用药,调节PCOS大鼠性激素、内分泌环境和抑制卵巢多囊样改变,其机制可能和改善胰岛素抵抗有关。

Objective To determine the effect of metformin and peony-glycyrrhiza decoction(PGD)on polycystic ovary syndrome(PCOS)in model rats.Methods The model was established by continuous intragastric administration of letrozole for 21 d.Fifty SD rats were randomly divided into the normal group,model group,metformin group,PGD group and combination group(n=10 each).After the drug intervention,the estrous cycle and morphological changes of ovaries in each group were determined.The levels of serum testosterone(T),estradiol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH),blood glucose,insulin,total cholesterol(TC),and leptin were measured by enzyme-linked immunosorbent assay(ELISA).The level of serum lactate was determined by lactic acid assay kit.Real-time quantitative PCR(RT-PCR)was used to measure the mRNA expression levels of insulin receptor and leptin receptor in ovarian tissue.Results Compared with the normal group,the disturbed estrous cycle and altered ovarian tissue structure were noted in the model group.The levels of serum T,LH,blood glucose,insulin,TC and leptin significantly increased(all P<0.05),whereas the levels of E2 and FSH significantly decreased(both P<0.05).The mRNA expression levels of ovarian insulin receptor and leptin receptor significantly decreased(both P<0.05).The level of serum lactate increased slightly,but there was no significant difference(P>0.05).Compared with the model group,the estrous cycle in each treatment group was resuming normal,and the ovarian tissue structure was improving.The levels of serum T,LH and insulin in the PGD group significantly decreased(all P<0.05),and the E2 level significantly increased(P<0.05),while there were no significant differences in the levels of glucose and lipid metabolism indexes such as blood glucose,TC and leptin(all P>0.05).The levels of serum insulin,blood glucose,TC and leptin significantly decreased in the metformin group(all P<0.05),and the mRNA expression levels of insulin receptor and leptin receptor in ovary significantly increased(P<0.05),but there were no significant differences in the levels of sex hormones such as T,LH and E2(all P>0.05).The levels sex hormone,glucose and lipid metabolism indexes were signifi cantly improved in the combination group. Conclusion Metformin and PGD may integrate the unique advantages of Chinese and Western medicine in regulating sex hormones and endocrine environment, and inhibit ovarian polycystic changes in PCOS rats. Its mechanism may be related to the improvement of insulin resistance.