细胞外信号调节激酶在多囊卵巢综合征患者子宫内膜中的活化及意义

Extracellular signal-regulated protein kinase activation in endometrium with polycystic ovary syndrome and its significance

目的 通过测定子宫内膜中胰岛素的丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路中ERK1/2（表示ERK1和ERK2,下同）的表达及其活化程度,探讨其在多囊卵巢综合征（PCOS）子宫内膜增生及癌变形成中的作用及意义,以及影响其表达及活化程度的因素.方法 选择2007年1月-2008年6月天津医科大学总医院行诊断性刮宫的PCOS患者52例（PCOS组）,相匹配的非PCOS患者（良性卵巢肿瘤）32例为对照组.测定所有观察对象的空腹血糖及胰岛素水平;所有观察对象均行子宫内膜病理检查,按子宫内膜病理结果将PCOS组患者分为子宫内膜增生及癌变组（19例）和正常子宫内膜组（33例）;根据是否存在胰岛素抵抗将PCOS组患者分为胰岛素抵抗组（38例）和非胰岛素抵抗组（14例）.蛋白印迹法（western blot）检测子宫内膜中ERK1/2及其活化形式--磷酸化ERK1/2（p-ERK1/2）蛋白的表达水平.结果 （1）PCOS组患者子宫内膜中p-ERK1/2蛋白的表达水平[（61±13）%]高于对照组[（44±10）%],两组比较,差异有统计学意义（P＜0.01）.（2）子宫内膜增生及癌变组子宫内膜中p-ERK1/2蛋白的表达水平[（70±11）%]高于正常子宫内膜组[（55±10）%],两组比较,差异有统计学意义（P＜0.01）;胰岛素抵抗组子宫内膜中p-ERK1/2蛋白的表达水平[（63±13）%]高于非胰岛素抵抗组[（55±7）%],两组比较,差异有统计学意义（P＜0.01）.（3）空腹胰岛素水平、胰岛素曲线下面积、体质指数与PCOS组患者子宫内膜中p-ERK蛋白的表达水平相关,相关系数分别为0.447、0.456、0.381（P均＜0.01）.结论 PCOS患者子宫内膜存在MAPK/ERK信号通路的过度活化,与子宫内膜增生及癌变的发生有关;胰岛素抵抗及高胰岛素血症有促进ERK活化的作用.

Objective To investigate the activation of mitogen-activated protein kinase （MAPK）/extracellular signal-regulated protein kinase （ERK） signaling pathway in the endometrium of women with polycystic ovary syndrome （PCOS） and its effect and significance in the cause of hyperplasia and carcinoma;and investigate the factors which affect the activation of the MAPK/ERK signaling pathway. Methods Collected 52 patients diagnosed as PCOS who were taken dilation and curettage of uterus as study, while 32 non-PCOS patients matched as control group. Serum hormonal parameters, fasting blood glucose and insulin were measured in all patients. The PCOS patients were sub-group as insulin resistance group and non-insulin resistance group; all the patients were carried out pathology inspection of endometria, and the PCOS patients were sub-group as endometrial hyperplasia and carcinoma group and normal endometrium group based on the outcome of pathology inspection. Western blot were performed to detect the expressions of ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2）, the activation of ERK1/2. Results （1）The expression of pERK1/2 [（61 ±13）%] in the endometrium in PCOS group was higher than that in the control [（44 ±10）%, P ＜0.01]. （2）The expression of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and carcinoma [ （ 70 ± 11 ）% ] compared to that in group of normal endometrium [ （55 ± 10）% ,P ＜ 0.01 ], while there were significant difference between group of insulin resistance [ （63 ± 13 ）% ] and group of non-insulin resistance [ （55 ±7）%, P ＜0.01 ]. （3） Fasting insulin level, insulin area under the curve and body mass index were related to the expression of p-ERK1/2 in endometrium with PCOS, the correlation coefficient were 0.447, 0.456 and 0.381, respectively （ all P ＜ 0.01 ）. Conclusions The MAPK/ERK signaling pathway in endometrium with PCOS was overactivation, which was related to the endometrial hyperplasia and carcinoma; while the activation of MAPK/ERK signaling pathway were effected by insulin resistance and hyperinsulinemia.