来曲唑配合高脂膳食诱导胰岛素抵抗多囊卵巢综合征大鼠代谢表型的实验研究

Glucose and lipid metabolism in Letrozole and high-fat diet induced PCOS-IR rats

摘要:

目的  建立来曲唑及高脂饲料诱导的大鼠多囊卵巢综合征（PCOS）胰岛素抵抗（IR）动物模型，探讨其生殖内分泌异常及代谢表型特征。方法  将24只3周龄雌性SD大鼠随机分为PCOS-IR组、PCOS组、高脂组、对照组，每组6只。PCOS-IR组予高脂饲料喂养12周，第6周龄时开始每日灌胃来曲唑羧甲基纤维素钠（CMC-Na）溶液，连续9周；PCOS组常规饲料喂养12周，第6周龄时开始每日灌胃来曲唑CMC-Na溶液，连续9周；高脂组予高脂饲料喂养12周，第6周龄时开始每日灌胃0.5%CMC-Na溶液，连续9周；对照组常规饲料喂养12周，第6周龄时开始每日灌胃0.5%CMC-Na溶液，连续9周。观察体重和卵巢组织学变化，测定血脂水平、糖耐量、胰岛素耐量、空腹血糖（FPG）和空腹胰岛素（FINS）浓度，并计算胰岛素抵抗指数（HOMA-IR）。结果  PCOS-IR组和PCOS组卵巢呈多囊样改变，卵巢闭锁卵泡增多，闭锁卵泡的直径较大，颗粒细胞层数有所减少，未见黄体分布；高脂组及对照组卵巢分布有各级卵泡，可见较多黄体分布。与对照组比较，PCOS-IR组的体重增加（P =0.000），总胆固醇升高（P <0.05），低密度脂蛋白升高（P <0.01），糖耐量曲线下面积（AUC）增加（P <0.05），胰岛素耐量AUC增加（P <0.01），FINS升高（P <0.01），HOMA-IR升高（P <0.05）。结论  来曲唑合并高脂膳食可成功诱导胰岛素抵抗PCOS大鼠典型的代谢表型。

Abstract:

Objective To investigate glucose and lipid metabolism in Letrozole and high-fat diet (HFD) induced polycystic ovary syndrome-insulin resistance (PCOS-IR) rats. Methods Twenty-four female SD rats of 3 weeks were randomly divided into 4 groups: control group, HFD group, PCOS group and PCOS-IR group. The rats in the HFD group and the PCOS-IR group were fed with high-fat diet for 12 weeks, while those of the control group and PCOS group were fed with normal diet. At the age of 6 weeks, the PCOS and PCOS-IR groups received Letrozole intragastric administration for 9 weeks. The changes in weight and ovarian morphology were observed; blood lipid, blood fasting plasma glucose (FPG), blood fasting insulin (FINS) and homeostasis model of assessment for insulin resistence index (HOMA-IR) were determined; and intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test were conducted in all the groups. Results Compared with the control and HFD groups, the PCOS and PCOS-IR groups showed polycystic ovaries with high incidence of atretic follicle and ovarian cyst together with decreased layers of granulosa cells and no corpora lutea. Compared with the control group, the PCOS-IR group exhibited increased weight (P = 0.000) with higher total cholesterol concentration (P < 0.05) and low-density lipoprotein concentration (P < 0.01), and increased AUC of IPGTT (P < 0.05) and AUC of insulin tolerance (P < 0.01). The PCOS-IR group also showed higher FINS concentration (P < 0.01) and increased HOMA-IR (P < 0.05). Conclusions Letrozole and high-fat diet can successfully induce typical metabolic phenotypes of insulin resistance in PCOS-IR rats.