来曲唑联合高糖高脂饮食构建多囊卵巢综合征伴胰岛素抵抗大鼠模型研究

doi:10.3969/j.issn.1006-7795.2021.03.016

首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (3): 436-442.doi: 10.3969/j.issn.1006-7795.2021.03.016

来曲唑联合高糖高脂饮食构建多囊卵巢综合征伴胰岛素抵抗大鼠模型研究

王景尚, 尹晓丹, 何军琴, 武颖, 张莹, 李宪锐

首都医科大学附属北京妇产医院中医科,北京 100026

收稿日期:2020-04-21 出版日期:2021-06-21 发布日期:2021-06-16
基金资助:
北京市医院管理局登峰人才培养计划(DFL20151301),首都中医药研究专项(16ZY18),首都医科大学附属北京妇产医院中青年学科骨干培养专项(fcyy201508)。

Experimental study on establishment of polycystic ovary syndrome rat model with insulin resistance by letrozole combined with high-sugar and high-fat diet

Wang Jingshang, Yin Xiaodan, He Junqin, Wu Ying, Zhang Ying, Li Xianrui

Department of Traditional Chinese Medicine,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China

Received:2020-04-21 Online:2021-06-21 Published:2021-06-16
Supported by:
Beijing Municipal Administration of Hospitals’Ascent Plan (DFL20151301), Capital Chinese Medicine Research Project(16ZY18), Young and Middle-aged Discipline Backbone Training Project of Beijing Obstetrics and Gynecology Hospital, Capital Medical University(fcyy201508).

摘要/Abstract

摘要： 目的探讨应用来曲唑联合高糖高脂饮食的方法构建多囊卵巢综合征伴胰岛素抵抗(polycystic ovarian syndrome-insulin resistance,PCOS-IR)大鼠模型。方法 6周龄雌性SD大鼠20只,普通饲料适应性喂养1周后,随机数字表法选取10只作为对照组,其余10只作为模型组。对照组给予普通饲料,模型组给予高糖高脂饲料喂养28 d。于喂养第8天,模型组大鼠开始每日用0.4 mL溶于1%(质量分数)羧甲基纤维素溶液(carboxymethyl cellulose solution,CMC)的来曲唑液(1 mg·kg^-1·d^-1)灌胃,对照组灌服等体积CMC溶液,连续灌胃21 d。自灌胃第7天起,每日晨行阴道涂片,观察阴道脱落细胞的周期变化,判断动情周期,直至实验结束。灌胃结束后,测量体质量,尾静脉采血测定大鼠空腹血糖(fasting blood glucose,FBG),ELISA法测定血清促黄体生成素(luteinizing hormone,LH)、促卵泡生成素(follicle stimulating hormone,FSH)、血清睾酮(testosterone,T)、空腹胰岛素(fasting insulin,FINS)浓度,并计算LH/FSH比值、胰岛素敏感指数(insulin sensitivity index,ISI)和胰岛素抵抗指数(insulin resistance index,HOMA-IR)。留取卵巢组织,应用HE染色观察卵巢组织形态。结果与对照组比较,模型组大鼠体质量、FBG、FINS、T、LH浓度、HOMA-IR指数、LH/FSH比值均明显升高,FSH及ISI浓度显著降低,差异均有统计学意义(P ＜ 0.01);阴道涂片显示,模型组大鼠动情周期均消失;对照组卵巢局部组织形态正常,模型组呈典型多囊样改变。结论应用高糖高脂联合来曲唑灌胃的方法,可以成功构建PCOS-IR大鼠模型,模型大鼠出现明显的胰岛素抵抗、特征性的多囊卵巢组织及性激素改变。

关键词: 多囊卵巢综合征, 胰岛素抵抗, 来曲唑, 高糖高脂饮食, 大鼠模型

Abstract: Objective To establish a rat model of polycystic ovary syndrome with insulin resistance (PCOS-IR) by using letrozole combined with high-fat and high-sugar diet. Methods After one week of adjustable feeding, twenty 6-week-old female SD rats were randomly divided into 2 groups:10 rats as control group, the other 10 as model group. Rats in control group were fed with ordinary diet, while model group with high-sugar and high-fat diet for 28 days. From the 8th day, the rats in model group received 0.4 mL letrozole (1 mg/kg) daily for 21 consecutive days and fed with high-sugar and high-fat diet, while rats in control received 0.4 mL 1% carboxymethyl cellulose solution daily and fed with standard diet. The vaginal smear was examined every morning to observe the vaginal exfoliated cell changes from the 15th day to the end of experiment. After lavage, fasting blood glucose (FBG) was measured from caudal vein. The levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) and fasting insulin (FINS) were measured and the LH/FSH ratio, insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated. The changes of body weight and ovarian histological phenotypes were observed. Results Compared with the control group,the body weight, the levels of FBG, FINS, T, LH, HOMA-IR, and LH/FSH ratio all increased significantly in model group, while the FSH and ISI levels in the model group decreased significantly,the difference were all statistically significant (P<0.01). The vaginal smear showed that the estrus cycle disappeared in the model group. The local ovarian tissue morphology was normal in the control group, while the model group expressed typically polycystic changes. Conclusion Letrozole combined with high-sugar and high-fat diet can successfully induce PCOS-IR rat model with typical polycystic changes, insulin resistance and endocrine abnormality.

Key words: polycystic ovary syndrome, insulin resistance, letrozole, high-sugar and high-fat diet, rat model

中图分类号:

R-332

王景尚, 尹晓丹, 何军琴, 武颖, 张莹, 李宪锐. 来曲唑联合高糖高脂饮食构建多囊卵巢综合征伴胰岛素抵抗大鼠模型研究[J]. 首都医科大学学报, 2021, 42(3): 436-442.

Wang Jingshang, Yin Xiaodan, He Junqin, Wu Ying, Zhang Ying, Li Xianrui. Experimental study on establishment of polycystic ovary syndrome rat model with insulin resistance by letrozole combined with high-sugar and high-fat diet[J]. Journal of Capital Medical University, 2021, 42(3): 436-442.

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来曲唑联合高糖高脂饮食构建多囊卵巢综合征伴胰岛素抵抗大鼠模型研究

Experimental study on establishment of polycystic ovary syndrome rat model with insulin resistance by letrozole combined with high-sugar and high-fat diet

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