多囊卵巢综合征患者子宫内膜组织中胰岛素PI3K／Akt信号通路的活化及其意义

Activation and significance of the PI3K/Akt pathway in endometrium with polycystic ovary syndrome patients

目的通过分析多囊卵巢综合征（pcos）患者子宫内膜组织中胰岛素的磷脂酰肌醇3激酶（P13K）／蛋白激酶B（Akt）信号通路中Akt的表达及其活化程度，探讨P13K／Akt信号通路活化在PCOS子宫内膜增生及癌变形成中的作用及意义，并分析影响该信号通路活化程度的因素。方法选择2007年1月—2008年6月在天津医科大学总医院就诊的PCOS患者52例为PCOS组，非PCOS（输卵管因素不孕或卵巢良性肿瘤）患者32例为对照组；测定所有患者的血清生殖激素水平、空腹血糖及胰岛素水平，并取子宫内膜组织行病理检查；计算体质指数（BMI）、稳态模型评估法计算的胰岛素抵抗指数（HOMA-IR）。对PCOS组患者根据病理检查结果分为正常子宫内膜、子宫内膜增生及癌变，根据是否存在胰岛素抵抗分为胰岛素抵抗和非胰岛素抵抗。蛋白印迹法检测子宫内膜组织中Akt、磷酸化Akt（p-Akt）蛋白的表达水平。结果（1）PCOS组患者子宫内膜组织中p-Akt蛋白的表达水平[（46±18）％]高于对照组[（33±9）％]，两组比较，差异有统计学意义（P〈0．01）。（2）PCOS组子宫内膜增生及癌变患者子宫内膜组织中p-Akt蛋白的表达水平[（56±19）％]高于正常子宫内膜者[（31±12）％]，两者比较，差异有统计学意义（P〈0．05）；胰岛素抵抗患者子宫内膜组织中p-Akt蛋白的表达水平[（50±19）％]高于非胰岛素抵抗者[（34±10）％]，两者比较，差异有统计学意义（P〈0．01）。（3）HOMA-IR、BMI与子宫内膜组织中p-Akt蛋白的表达水平呈正相关（r=0．400、0．326，P均〈0．05）。结论PCOS患者子宫内膜存在胰岛素PBK／Akt信号通路的过度活化，该信号通路过度活化与PCOS子宫内膜增生及癌变有关。胰岛素抵抗、肥胖可能是影响子宫内膜组织中胰岛素PI3K／Akt信号通路过度活化的独立风险因素。

Objective To investigate activation of the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway in the endometrium of women with polycystic ovary syndrome （PCOS） and its role in endometrium hyperplasia and carcinogenesis, and the factors affecting the activation of the PI3K/Akt pathway. Methods From Jan 2007 to Jun 2008, 52 patients with PCOS who underwent dilatation and curettage were selected as experimental group matched with 32 non-PCOS patients as control group. Serous hormonal parameters, fasting blood glucose and insulin, body mass index （BMI）, and endometrium pathology were measured and evaluated in all patients. The PCOS patients were divided into insulin resistance and non-insulin resistance group according to homeostasis model assessment-insulin resistance index （HOMA-IR）. Meanwhile, the PCOS patients were grouped as normal, endometrial hyperplasia andcarcinoma depending on outcome of pathology. The expression of Akt and phosphorylated Akt （p-Akt） were determined by western blot. Results （ 1 ） The expression of p-Akt was significantly higher in PCOS group [（46＋18）%] than that in control [（33±9）%, P 〈0.01）]. （2） The expression of p-Akt was significantly higher in group of endometrial hyperplasia and carcinoma [ （56 ＋ 19）% ] when compared with those in normal endometria group [ （31± 12）%, P 〈 0. 05 ]; the expression of p-Akt was significantly higher in group of insulin resistance [ （50± 19）% ] compared with that in non-insulin resistance group [ （34 ± 10）%, P 〈0. 011. （3） There was a positive correlation between the expression level of p-Akt in endometrium with PCOS and HOMA-IR and BMI respectively （r =0. 400, 0. 326, both P 〈0. 05）. Conclusions The PI3K/Akt pathway was over activated in endometrium with PCOS which may be associated with the formation of endometrial hyperplasia and carcinoma in PCOS patients. Insulin resistance and obesity may be high risk factors for over-activation of the PI3K/Akt pathway in endometrium with PCOS.