来曲唑联合高脂膳食诱导PCOS-IR大鼠模型复制时间及其内分泌、代谢改变的实验研究

Experimental study on model replication time, endocrine and metabolic changes in rats with PCOS-IR induced by letrozole combined with high fat diet

目的研究多囊卵巢综合征胰岛素抵抗(PCOS-IR)大鼠理想模型复制时间及其内分泌、代谢等病理改变。方法对照组大鼠予普通饲料,每日灌胃羧甲基纤维素钠溶液;模型组大鼠予高脂饲料,每日灌胃来曲唑加羧甲基纤维素钠溶液。根据喂养时间,每组在第21、24、27及30天处死6只。观察两组大鼠的体重、卵巢体积和组织学变化、内分泌与代谢指标。检测大鼠空腹血糖(FBG),ELISA法检测大鼠性激素水平、甘油三酯(TG)及空腹胰岛素(FINS);计算卵巢指数、促卵泡激素(FSH)/黄体生成素(LH)比值及胰岛素抵抗指数(HOMA-IR)等。结果模型组各时间点大鼠体重均高于对照组(P<0.05),其中第27和30天大鼠体重及Lee’s指数均高于第21天(P<0.05)。肉眼可见模型组大鼠卵巢体积增大(P<0.05),卵巢表面可见较多密集的透明囊状扩张卵泡,镜下卵巢呈多囊样改变;模型组第30天大鼠的卵巢体积大于第21天(P<0.05)。模型组各时间点大鼠血清TG、FSH/LH比值、T水平较对照组升高(P<0.05);模型组第27和30天大鼠血清FINS及HOMAIR较同时间点对照组升高(P<0.05)。结论来曲唑联合高脂膳食连续喂养27 d可成功复制符合PCOS-IR病理特征及内分泌、代谢紊乱的大鼠模型。

Objective To explore the ideal model replication time and pathological changes of endocrine and metabolism in PCOS-IR(polycystic ovary syndrome with insulin resistance) rats. Methods The control group rats were fed with normal diet, and administered by the 0.5% carboxymethylcellulose sodium salt sodium(CMCNa) daily. The model group rats were given a high-fat diet with 60% fat content, and the letrozole solution was administered daily. According to the feeding time, each group was subdivided into four subgroups on the 21 st, 24 th, 27 th and 30 th day, six in each subgroup. The body mass, ovarian volume and ovarian histological changes, endocrine and metabolic indicators were observed in each group. After fasting, the rats were tested for fasting blood-glucose(FPG). The rat serum ELISA kit was used to determine the sex hormone level, triglyceride(TG) and fasting insulin(FINS) levels, calculate ovarian index, Follicle stimulating hormone(FSH)/Luteinizing hormone(LH) ratio and insulin resistance index(homeostasis model of assessment for insulin resistence index, HOMA-IR). Results The body weight of the rats in the model group was significantly higher than that in the control group(P<0.05). The body mass and Lee’s index of the 27 th d and 30 th d model groups were significantly higher than the 21 st d. The ovarian volume of the model group was significantly increased(P<0.05), and ovarian volume of the 30 th d was significantly higher than the 21 st d(P<0.05), and the ovarian surface was more visible. The dense vesicle-like dilated follicles showed polycystic changes in the ovary. The serum FSH/LH ratio and T level were significantly increased in each model group(P<0.05). In addition, serum TG was significantly increased(P<0.05);Rats at the 27 th d and 30 th d model groups showed a significant increase in FINS and HOMA-IR(P<0.05). Conclusion The rat model of PCOSIR pathological features and endocrine and metabolic disorders was successfully established by continuous feeding of letrozole combined with high-fat diet for 27 days.