| 二甲双胍改善多囊卵巢综合征大鼠胰岛素敏感性的机制 |
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| 引用本文： | 张二红,黎小妍,徐 芬,张添松,古 健. 二甲双胍改善多囊卵巢综合征大鼠胰岛素敏感性的机制[J]. 中山大学学报(医学科学版), 2014, 35(6): 839 |
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| 作者姓名： | 张二红 黎小妍 徐 芬 张添松 古 健 |
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| 作者单位： | 中山大学附属第三医院1. 不育与性医学科,2. 药剂科,3. 内分泌与代谢病科,4. 妇科,广东 广州 510630 |
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| 基金项目： | 广东省科技计划项目(2007B060401018,2009B030801103);广东省医学科研基金(B2010095);拜耳医药保健有限公司2011横向课题 |
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| 摘 要： | 摘 要: 【目的】 探讨二甲双胍对多囊卵巢综合征(PCOS)大鼠胰岛素敏感性的作用及机制?【方法】 应用脱氢表雄酮制备PCOS大鼠模型20只,随机分为二甲双胍干预组?PCOS组各10只,同批大鼠设为正常对照组10只?干预前后检测大鼠胰岛素抵抗水平,酶法检测肝脏组织甘油三酯含量,Western blot法检测葡萄糖调节蛋白78 (GRP78)?固醇调节元件结合蛋白-1c(SREBP-1c)和磷酸化AMPKa蛋白(P-AMPKa)的表达变化?【结果】 PCOS 组大鼠表现明显胰岛素抵抗,肝脏组织甘油三酯含量?GRP78和SREBP-1c蛋白表达水平显著高于正常对照组(P < 0.05)?二甲双胍干预后PCOS大鼠胰岛素抵抗明显改善,且其明显抑制了PCOS大鼠肝脏甘油三酯含量升高(P < 0.05)以及GRP78和SREBP-1c蛋白表达的增高(P < 0.05),二甲双胍干预后上述指标与正常组无统计学差异?PCOS 组大鼠肝脏P-AMPKa蛋白表达显著低于正常对照组(P < 0.05),二甲双胍治疗后肝脏P-AMPKa蛋白表达增至正常对照组水平?【结论】 二甲双胍改善PCOS 大鼠胰岛素抵抗和肝脏脂肪沉积,可能与其激活肝脏组织AMPK通路和降低内质网应激水平有关?
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| 关 键 词： | 二甲双胍 PCOS 胰岛素抵抗 肝脏 |
| 收稿时间： | 2014-06-06 |
Metformin Improves Insulin Sensitivity of Rat Model with Polycystic OvarySyndrome and Its Mechanism |
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| ZHANG Er-hong,LI Xiao-yan,XU Fen,ZHANG Tian-song,GU Jian. Metformin Improves Insulin Sensitivity of Rat Model with Polycystic OvarySyndrome and Its Mechanism[J]. Journal of Sun Yatsen University(Medical Sciences), 2014, 35(6): 839 |
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| Authors: | ZHANG Er-hong LI Xiao-yan XU Fen ZHANG Tian-song GU Jian |
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| Affiliation: | 1. Department of Infertility and Sexual Medicine; 2. Department of Pharmacy; 3. Department of Endocrinology and Metabolism; 4. Department of Gynaecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China |
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| Abstract: | Abstract: 【Objective】 To investigate the effects of metformin on insulin sensitivity and possible mechanism in rats with polycystic ovary syndrome (PCOS). 【Methods】 PCOS rat model was induced by subcutaneous injecting dehydroeplandrosterone up to 20 days and then divided randomly into PCOS and metformin group. The rats of metformin group were intragastrically given metformin 140 mg?kg-1?d-1 for 15 days. Blood were collected to test free glucose and insulin levels before and after metformin intervention. Liver tissues were collected to test triglyceride content and protein expression. 【Results】 PCOS rats exhibit insulin resistance and metformin treatment can improve insulin sensitivity in PCOS rats. Triglyceride levels, GRP 78 and SREBP-1c protein expression in the liver of PCOS rats were higher than those of the controls, whereas P-AMPKa protein expression was lower than that of the normal controls (P < 0.05). After the treatment of metformin, triglyceride levels, GRP 78 and SREBP-1c protein expression in the liver of PCOS rats were significantly decreased (P < 0.05) and P-AMPKa protein expression was increased to the level similar with that of normal controls. 【Conclusion】 Metformin protect PCOS rats against insulin resistance and hepatocyticf at deposition largely through effects on activating AMPK pathway and on decreasing endoplasmic reticulum stress in liver. |
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| Keywords: | metformin polycystic ovarian syndrome insulin resistance liver |
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