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目的:探讨脱氢表雄酮(dehydroepiandrosterone,DHEA)诱导的SD大鼠多囊卵巢综合征(polycystic ovarian syndrome,PCOS)模型效果,检测该模型中雄激素受体(androgen receptor,AR)与共激活因子相关的精氨酸甲基转移酶1(coactivator-associated arginine methyltransferase 1,CARM1)表达情况,研究PCOS模型中胰岛素抵抗、激素改变、AR与CARM1及其产物非对称二甲精氨酸(asymmetric dimethylarginines,ADMA)之间的关系。方法:将40只23日龄雌性SD大鼠随机分为实验组和对照组,每组20只,实验组每日皮下注射DHEA 0.6 mg/kg,对照组同时同位置注射等量注射用油。连续20 d后观察大鼠卵巢组织学形态及体质量、性激素、空腹血糖、胰岛素(insulin,Ins)及血清ADMA变化,评价胰岛素抵抗情况,并用免疫组化确定CARM1在卵巢组织中的表达情况,Western blot及荧光定量PCR检测卵巢AR、CARM1蛋白及m RNA转录表达情况。结果:PCOS实验组最终体质量、增加体质量、卵巢重量均明显高于对照组(P<0.05);血清空腹血糖、胰岛素、胰岛素抵抗指数(homeostasis model assessment index,HOMA index)、ADMA、睾酮(testosterone,T)、雌二醇(estrodiol,E2)均明显高于对照组(P<0.05);实验组卵巢出现大量闭锁卵泡、囊状卵泡,颗粒细胞层减少,卵母细胞消失等特征;卵巢组织中的CARM1主要由颗粒细胞表达;AR、CARM1蛋白量及m RNA表达量实验组明显高于对照组(P<0.05)。结论:CARM1及其产物ADMA与PCOS高雄激素血症、排卵功能障碍和胰岛素抵抗之间存在相关性,但二者与PCOS上述三大病理生理特点之间的内在联系及其具体机理仍需要进一步验证。
OBJECTIVE: To investigate the effect of dehydroepiandrosterone (DHEA) -induced polycystic ovarian syndrome (PCOS) in SD rat model and to detect the expression of androgen receptor (AR) and coactivator Related arginine methyltransferase 1 (CARM1) expression in PCOS model of insulin resistance, hormone changes, AR and CARM1 and its product asymmetric dimethylarginines (asymmetric dimethylarginines, ADMA) the relationship between. Methods: Forty three-day-old female Sprague-Dawley rats were randomly divided into experimental group and control group, with 20 rats in each group. DHEA 0.6 mg / kg was subcutaneously injected into the experimental group, while the control group was equally injected with the same amount of injection oil. The ovarian tissue morphology, body weight, sex hormones, fasting blood glucose, insulin and serum ADMA were observed after 20 days of continuous operation to evaluate the insulin resistance. The expression of CARM1 in ovarian tissue was determined by immunohistochemistry, The expression of AR, CARM1 protein and m RNA in ovary were detected by Western blot and real-time PCR. Results: The body mass, weight gain and ovary weight in PCOS group were significantly higher than those in control group (P <0.05). Serum fasting blood glucose, insulin, HOMA index, ADMA and testosterone testosterone, T) and estrodiol (E2) were significantly higher than those in the control group (P <0.05). A large number of atresia follicles and cystic follicles were found in the ovary of the experimental group, and the number of granulocyte layers and oocytes disappeared. CARM1 was mainly expressed in granulosa cells. The contents of AR, CARM1 and m RNA in experimental group were significantly higher than those in control group (P <0.05). CONCLUSION: There is a correlation between CARM1, its product ADMA and hyperandrogenism, ovulation dysfunction and insulin resistance in PCOS. However, the intrinsic relationship between the two and PCOS pathophysiological characteristics still need further verification .