多囊卵巢综合征骨骼肌胰岛素抵抗大鼠模型的建立

Establishment of rat models of polysystic ovarian syndrome characterized by skeletal muscle insulin resistance

背景:研究表明胰岛素抵抗在多囊卵巢综合征的发生与发展过程中起重要作用,建立理想的多囊卵巢综合征骨骼肌胰岛素抵抗动物模型是研究该疾病的基础。目的:探讨建立较为理想的多囊卵巢综合征骨骼肌胰岛素抵抗大鼠模型的方法。方法:将八九周龄SD雌性大鼠随机分为模型组和对照组。模型组给予胰岛素联合人绒毛膜促性腺激素皮下注射,并以高脂饲料和50g/L葡萄糖水喂养,对照组皮下注射生理盐水,常规饮食喂养。结果与结论:造模6周后,模型组大鼠卵巢体积明显增大,且呈多囊性改变;血清睾酮、黄体生成素、空腹血糖和胰岛素水平高于对照组;骨骼肌组织中葡萄糖转运蛋白4表达明显低于对照组,且其葡萄糖转运蛋白4阳性颗粒靠近骨骼肌细胞膜边缘者较少。可见胰岛素联合人绒毛膜促性腺激素皮下注射,并饲以高脂饲料和50g/L葡萄糖水是建立多囊卵巢综合征骨骼肌胰岛素抵抗大鼠模型较为理想的方法。

BACKGROUND：Studies have demonstrated that insulin resistance plays an important role in the occurrence and development of polycystic ovarian syndrome（PCOS）.Establishing rat models of PCOS characterized by skeletal muscle insulin resistance is the basis for studying PCOS.OBJECTIVE：To establish the ideal rat models of PCOS characterized by skeletal muscle insulin resistance.METHODS：Female Sprague-Dawley rats,aged 8-9 weeks,were randomized to model group and control group with 20 animals in each group.Insulin and human chorionic gonadotrophin were administered to the model group rats which were fed with high fat diet and 50 g/L glucose solution.The rats in the control group were given normal diet and injected normal saline daily.After 6 weeks of treatment,the body weight was measured and then all of rats were sacrificed.Ovaries were taken out for histological observation.Serum concentrations of estradiol,testosterone,progestogen,follicle-stimulating hormone and luteinizing hormone were detected.Fasting blood glucose and insulin levels were measured for evaluating the insulin resistance.The expression of glucose transporter 4 in the skeletal muscle was detected by immunohistochemical staining.RESULTS AND CONCLUSION：The ovarian size in the model group was larger than that in the control group.The ovaries of the model group showed multiple follicular cysts.The fasting blood glucose,fasting insulin,testosterone and luteinizing hormone levels in the model group were respectively higher than those in the control group.While,the expression of glucose transporter 4 in PCOS rats was significantly lower than that of the control group.In model group,the intracytoplasmic granules of glucose transporter 4 were mostly located in the cytoplasm,however,in the control group,they were near the muscle cellullar membrane.Therefore,the administration of insulin and human chorionic gonadotrophin combined with high fat diet and 50 g/L glucose solution is an ideal method to establish the rat models of PCOS with significant muscle insulin resistance.