颗粒蛋白前体在高脂饮食诱导的肥胖PCOS大鼠卵巢中的表达

摘要

目的 研究颗粒蛋白前体(PGRN)在肥胖PCOS大鼠卵巢中的表达情况,初步探讨PGRN在PCOS发病中的作用. 方法 选择SPF级23日龄SD雌性大鼠38只,使用随机数字表随机分为3组:正常对照组(n=8)、PCOS组(DHEA组,n=15)及肥胖PCOS组(DHEA+HFD组,n=15).采用脱氢表雄酮联合高脂饲料(DHEA+ HFD)诱导肥胖PCOS大鼠.HE染色光镜下观察PCOS大鼠卵巢的病理结构改变.酶联免疫吸附法测定血清睾酮(T)、雌二醇(E2)及空腹血糖(FBG)、空腹胰岛素(FINS)含量等,比较各组间的水平差异.采用免疫组织化学法检测各组卵巢PGRN的表达水平及分布情况. 结果 造模结束时,DHEA+ HFD组体重显著高于对照组(P＜0.01)及DHEA组(P＜0.05).DHEA组及DHEA+ HFD组的FINS、稳态模型评估的胰岛素抵抗指数(HOMA IR)均显著高于对照组(P＜0.05).DHEA组及DHEA+ HFD组的睾酮(T)、FSH水平均显著升高(P＜0.01).DHEA组及DHEA+ HFD组卵巢组织光镜下均表现出典型的多囊样改变.免疫组化结果显示各组大鼠卵巢中均可见PGRN蛋白表达,主要分布于卵泡的颗粒细胞层及黄体;DHEA组PGRN表达水平显著高于对照组(P＜0.01),DHEA+ HFD组PGRN表达水平显著高于DHEA组及对照组(P＜0.01). 结论 PGRN在卵巢颗粒细胞层有表达.其在PCOS大鼠和肥胖PCOS大鼠卵巢组织中的差异性表达,提示PGRN可能通过作用于局部卵泡微环境,参与PCOS肥胖及慢性代谢性炎症的发生.%Objective:To investigate the expression of progranulin (PGRN) in ovary in high diet induced overweight rats with polycystic ovary syndrome (PCOS).Methods:Thirty eight rats aged 23 days were divided into three groups:normal control group (n=8),DHEA group (n=15) and overweight PCOS group (DHEA+HFD,n=15).The overweight PCOS female rats were induced by dehydroepiandrosterone combined with high fat diet (DHEA+ HFD).The pathological changes of ovary of PCOS rats were observed by HE staining.Serum levels of testosterone (T),estradiol (E2) and fasting blood glucose (FBG),fasting insulin (FINS) were measured by enzymelinked immunosorbent assay.The expression level and distribution of PGRN in ovaries were detected by immunohistochemistry.Results:The weight of DHEA+HFDgroupwas significantly higher than that of control group (P＜ 0.01) and DHEA group (P＜0.05).The HOMA-IR in DHEA+HFD group and DHEA group was significantly higher than that in control group (P＜0.05).The ovaries of rats modeled by DHEA in two groups showed typical polycystic changes.Additionally,the expression of PGRN in granulose cell layer was significantly up regulated in DHEA and DHEA+ HFD groups compared with control group (P＜0.01),and the PGRN expression in DHEA+HFD group was significantly higher than DHEA group (P＜0.01).Conclusions:The expression of PGRN is up-regulated in the granulosa cells of the PCOS rats.Obesity can further induce PGRN up-regulated in the granulosa cells of PCOS rats.It indicates that the differential expression of PGRN may be related to the pathogenesis of PCOS obesity and chronic inflammation.