多囊卵巢综合征(PCOS)患者往往伴有卵巢细胞的胰岛素抵抗及激素水平的异常,胰岛素增敏剂能够缓解PCOS患者的症状。本研究利用地塞米松诱导的猪体外卵巢颗粒细胞胰岛素抵抗,探讨中药单体甘草次酸及水飞蓟宾作为胰岛素增敏剂对胰岛素抵抗卵巢颗粒细胞异常激素分泌的改善情况,从而阐明中药单体的疗效机制,进而扩大中药单体的临床应用。结果表明,地塞米松作用后,体外培养的猪卵巢颗粒细胞分泌睾酮(T)增加,同时伴有17α羟化酶(CYP17)mRNA表达量的上调,AMPK(一磷酸腺苷酸活化蛋白激酶)mRNA表达降低,芳香化酶(P450arom)变化不明显。甘草次酸和水飞蓟宾都能够通过提高AMPK mRNA的表达水平,降低胰岛素抵抗颗粒细胞的雄激素分泌能力及CYP17 mRNA的表达水平。结果显示,中药甘草次酸和水飞蓟宾显著抑制了胰岛素抵抗细胞过高的雄激素分泌能力。卵巢细胞AMPK途径的激活可能是中药胰岛素增敏剂治疗PCOS高雄激素血症的途径之一。

Ovarian cell Insulin Resistance (IR) and abnormal homogenesis is one of the characteristics of Polycystic Ovary Syndrome (PCOS) and could be remedied by the insulin sensitive agent. To investigate herbal medicine as insulin sensitive agents to improve IR ovarian granulosa cell in vitro and clarify the mechanism of herbal medicine on IR, glycyrrhetic acid and silibinin were used to treat dexamethasone (DEX) induced IR porcine ovary granulosa cells. After DEX treatment, the medium testosterone level increased, while the CYP17 mRNA expression increased and the AMP-activated protein kinase activity (AMPK), which is a protein that switches on ATP-producing catabolic pathways and switches off ATP-consuming anabolic processes based on energy status, mRNA expression decreased in vitro IR porcine ovarian theca cell. The results also show that compared to dexamethasone induced IR group, by adding glycyrrhetic acid and silibinin, testosterone production is reduced and mRNA expression of AMPK is increased. In summary, glycyrrhetic acid and silibinin significantly reverse hyperandorgen (testosterone) status and improve the sensitivity of energy balance by promoting the expression of AMPK. Chinese medicine glycyrrhetic acid and silibinin could reduce the hyperandrogenism of in vitro IR granulosa cell via increasing AMPK mRNA expression.