多囊卵巢综合征-胰岛素抵抗大鼠子宫组织中PPARs异常表达与胰岛素抵抗的关系  

Relationship Between the Abnormal Expression of PPARs and Insulin Resistance in Uterus of Rats with Polycystic Ovary Syndrome and Insulin Resistance

作　　者：魏巍 陈艺华 张秀智 冷义福 李纯 尹天晓 WEIWei;CHEN Yihua;ZHANG Xiuzhi;LENG Yifu;LI Chun;YIN Tianxiao(Reproductive Medicine Center,Affiliated Zhongshan Hospital of Dalian University,Dalian 116001,China;Dalian University,Dalian 116001,China)

机构地区：[1]大连大学附属中山医院生殖医学中心,大连116001 [2]大连大学,大连116001

出　　处：《实验动物与比较医学》2021年第5期435-442,共8页Laboratory Animal and Comparative Medicine

基　　金：大连市医学科学研究计划项目(1811101)。

摘　　要：目的探讨过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)在多囊卵巢综合征(polycystic ovarian syndrome,PCOS)伴胰岛素抵抗大鼠模型子宫组织中异常表达与胰岛素抵抗的关系。方法将40只雌性SD大鼠随机分为正常对照组和PCOS-胰岛素抵抗模型组,采用胰岛素+人绒毛膜促性腺激素(human chorionic gonadotrophin,hCG)皮下注射法建立大鼠PCOS-胰岛素抵抗模型,正常对照组注射等量生理盐水(即0.9%NaCl溶液)。应用ELISA检测两组大鼠空腹胰岛素和空腹血糖水平,并计算胰岛素抵抗指数。取大鼠子宫组织行HE染色,免疫组织化学法检测PPARs表达水平,蛋白质印迹法检测PPARs、胰岛素受体底物(insulin receptor substrate,IRS)、葡萄糖转运蛋白4(glucose transporter 4,GLUT-4)和胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)等蛋白表达。结果模型组大鼠血清空腹胰岛素、空腹血糖和稳态胰岛素评价指数显著高于正常对照组(P<0.05)。子宫组织HE染色提示,正常对照组大鼠子宫组织形态正常,模型组大鼠子宫内膜出现不同程度的增生性改变,腺腔变小,腺体数目减少,排列松散。免疫组织化学显示,PPARs的3种亚型PPARα、PPARβ及PPARγ在大鼠子宫组织中均有表达,模型组PPARα和PPARγ的表达下调(P<0.05),PPARβ在两组间的表达差异无统计学意义(P>0.05)。蛋白质印迹法检测结果显示,模型组大鼠子宫组织PPARα、PPARγ、IRS和GLUT-4的表达显著低于正常对照组(P<0.05),而IGF-1表达高于正常对照组(P<0.05)。结论在PCOS-胰岛素抵抗大鼠子宫组织中IRS、GLUT-4表达下调,而IGF-1表达上调,证实在子宫组织层面存在胰岛素抵抗,可能与PCOS大鼠子宫组织PPARα、PPARγ表达下调相关。Objective To investigate the relationship between abnormal expression of peroxisome proliferator-activated receptors(PPARs)and insulin resistance in the uterine tissues of rats with polycystic ovary syndrome and insulin resistance(PCOS-IR).Methods Forty female SD rats were randomly divided into normal control and PCOS-IR model groups.PCOS-IR models were established by subcutaneous injection of insulin and human chorionic gonadotropin(INS+hCG)method,and rats in the normal control group were injected with equal amounts of normal saline.Fasting insulin(FINS)and fasting plasma glucose(FPG)levels were measured by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Uterine tissues of rats were stained with hematoxylin-eosin(HE),PPARs were detected by immunohistochemistry,and the expressions of PPARs,insulin receptors(IRS),glucose transporter 4(GLUT-4),and insulin-like growth factor-1(IGF-1)were detected by Western blotting.Results FPG and FINS levels and HOMA-IR in the model group were significantly higher than those in the normal control group(P<0.05).HE staining of uterine tissues showed that the endometrium of the normal control group was normal,and the endometrium of the model group showed different degrees of proliferative changes,the glandular cavity became smaller,the number of glands decreased,and the arrangement was loose.Immunohistochemistry showed that three subtypes of PPARs(PPARα,PPARβ,and PPARγ)were expressed in the rat uterus.The expression of PPARαand PPARγin the rat uterus was down-regulated in the model group(P<0.05),and there was no significant difference in the expression of PPARβbetween the two groups(P>0.05).Western blotting results showed that the expression of PPARα,PPARγ,IRS,and GLUT-4 in the rat uterus of the model group was significantly lower than that of the normal control group(P<0.05),while the expression of IGF-1 was higher than that of the normal control group(P<0.05).Conclusion The expression of IRS and GLUT-4 is down-regulated and t

关 键 词：过氧化物酶体增殖物激活受体 多囊卵巢综合征 胰岛素抵抗 子宫组织 大鼠 

分 类 号：Q95-33[生物学—动物学] R711.75[医药卫生—妇产科学]