多囊卵巢综合征卵巢颗粒细胞凋亡调控蛋白Bcl-2、Bax、p53的表达及其意义

Expression and significance of apoptosis regulatory proteins Bcl-2, Bax and p53 in ovarian granulosa cells of patients with polycystic ovary syndrome

目的探讨多囊卵巢综合征(PCOS)卵巢颗粒细胞凋亡基因Bcl-2、Bax、p53的表达及意义。方法选择35例行腹腔镜下双侧卵巢打孔术的PCOS患者(PCOS组),另选择同期30例行腹腔镜妇科手术的非PCOS患者(对照组),收集术中取得的卵巢组织,通过免疫组织化学染色法检测2组卵巢颗粒细胞凋亡调控蛋白Bcl-2、Bax、p53分布与表达,计算组织学积分,比较PCOS患者术前及术后的卵泡刺激素、黄体生成素(LH)、雌二醇、睾酮水平,PCOS组患者术后规律服用二甲双胍1500mg/d,对其进行为期1年的随访,对比Bax阳性与Bax阴性患者的1年临床妊娠率差异。结果PCOS组患者的术后LH、睾酮均低于术前(P均<0.05)。PCOS组的Bax阳性颗粒细胞主要见于囊性卵泡壁,对照组Bax阳性颗粒细胞较少,散在分布于卵巢上皮间质。2组的Bcl-2阳性颗粒细胞数量均较少。PCOS组的p53阳性细胞主要散在分布于小卵泡壁,对照组的p53阳性细胞多为散在分布。PCOS组的Bax及p53蛋白的组织学积分均高于对照组(P均<0.05),2组Bcl-2蛋白的组织学积分比较差异无统计学意义(P>0.05)。35例PCOS患者中,Bax阳性28例、阴性7例,术后随访1年,Bax阳性者的1年临床妊娠率高于Bax阴性者(P<0.05)。结论凋亡调控蛋白Bax、p53可能参与PCOS患者卵巢颗粒细胞的凋亡。

Objective To investigate the expression and significance of apoptosis regulatory proteins Bcl-2, Bax and p53 in the ovarian granulosa cells of women with polycystic ovary syndrome( PCOS). Methods Thirty-five PCOS patients undergoing laparoscopic bilateral ovarian drilling( PCOS group) and 30 non-PCOS patients who underwent laparoscopic gynecologic surgery( control group) were recruited in this investigation. Ovarian tissues were collected during the operation. The distribution pattern and expression level of apoptosis regulatory proteins Bcl-2, Bax and p53 in the ovarian granulosa cells were detected by immunohistochemical staining in two groups, and the histological grading scores were calculated. The levels of follicle stimulating hormone, luteinizing hormone( LH), estradiol and tesosterone of PCOS patients were quantitatively measured and compared before and after operation. Patients in the PCOS group were given with metformin at a dose of 1 500 mg/d postoperatively and followed up for 1 year. The 1-year clinical pregnancy rate was statistically compared between patients with positive and negative Bax. Results The postoperative LH and testosterone levels in the PCOS group were significantly lower than those before operation( both P < 0.05). In the PCOS group, the Bax-positive granulosa cells were mainly distributed in the cystic follicular wall, whereas the quantity of Bax-positive granulosa cells was small and scattered in the ovarian epithelial stroma in the control group. The number of granulosa cells with positive Bcl-2 was small in both groups. In the PCOS group, p53-positive granulosa cells were mainly scattered in the wall of small follicles, whereas those in the control group were scattered. The histological grading scores of Bax and p53 proteins in the PCOS group were significantly higher than those in the control group( both P < 0.05), whereas the histological score of Bcl-2 protein did not significantly differ between two groups( P > 0.05). Among 35 PCOS patients, Bax was positive in 28 cases and negative in 7 cases. During 1-year follow-up, the 1-year clinical pregnancy rate of Bax-positive patients was significantly higher compared with that of those with negative Bax( P < 0.05). Conclusion Bax is probably involved in the apoptosis of ovarian granulosa cells in PCOS patients.