二甲双胍对子宫内膜异位症大鼠异位灶内VEGF和MMP9的影响研究
投稿时间:2016-07-17  修订日期:2016-07-25  点此下载全文
引用本文:程静,卢晓声,张慧娜,郝培培,吕杰强.二甲双胍对子宫内膜异位症大鼠异位灶内VEGF和MMP9的影响研究[J].医学研究杂志,2017,46(3):91-94
DOI: 10.11969/j.issn.1673-548X.2017.03.023
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作者单位E-mail
程静 325027 温州, 温州医科大学附属第二医院  
卢晓声 325027 温州, 温州医科大学附属第二医院  
张慧娜 325027 温州, 温州医科大学附属第二医院  
郝培培 325027 温州, 温州医科大学附属第二医院  
吕杰强 325027 温州, 温州医科大学附属第二医院 Jieqianglu@126.com 
基金项目:浙江省重点科技创新团队基金资助项目(2011R50013)
中文摘要:目的 探讨盐酸二甲双胍(metformin)对子宫内膜异位症(EM)大鼠模型内异灶体积、内异灶内VEGF和MMP9的表达的影响,探讨二甲双胍治疗EM的可行性。方法 50只SD大鼠自体移植方法建立EM大鼠模型,在造模成功后,给予EM大鼠亮丙瑞林每21天1mg/kg皮下注射和二甲双胍灌胃治疗,二甲双胍治疗分为高剂量[200mg/(kg·d)]、中剂量[100mg/(kg·d)]和低剂量组[50mg/(kg·d)]。二甲双胍连续用药42天后处死内异症大鼠,取内异灶,测量内异灶体积,免疫组化、蛋白印迹法检测内异灶内的VEGF和MMP-9的表达。结果 内异灶体积∶3种二甲双胍剂量组与亮丙瑞林组内异症大鼠内异灶体积显著小于对照组(P<0.05)。免疫组化评分的结果提示∶用药42天后,中剂量、低剂量二甲双胍组和亮丙瑞林组(P<0.05)显著降低内异灶内VEGF的表达,与对照组相比,差异有统计学意义(P<0.05);二甲双胍的3种剂量组和亮丙瑞林组均显著降低内异灶内MMP9的表达,与对照组相比差异均有统计学意义(P<0.05)。蛋白印迹实验结果提示∶中剂量二甲双胍组显著抑制内异灶内VEGF的表达(P<0.05),而低剂量、高剂量二甲双胍和亮丙瑞林组并未抑制内异灶内的VEGF的表达(P>0.05);中、高剂量二甲双胍组均能显著抑制内异灶内MMP9的表达(P<0.05),低剂量二甲双胍和亮丙瑞林组并未抑制内异灶内的MMP9表达。结论 盐酸二甲双胍可以显著抑制子宫内膜异位症大鼠内异病灶,降低内异灶内VEGF和MMP9的表达,有望成为治疗子宫内膜异位症的新方法。
中文关键词:子宫内膜异位症  盐酸二甲双胍  血管内皮生长因子  基质金属蛋白酶-9
 
Effects of Metformin on Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinase-9 (MMP-9) Expression of Endometriotic Lesions from Rats with Endometriosis
Abstract:Objective To determine the role of metformin on volume of endometriotic lesions, on MMP-9 and VEGF expression of endometriotic lesions from rats with endometriosis. Methods Fifty SD rats with endometriosis were established by autologous transplantation method,and then were randomly divided into 5 groups:control group, GnRHa group[1mg/(kg·21d)], treatment with high dose metformin[200mg/(kg·d)],middle dose metformin[100mg/(kg·d)],low dose metformin[50mg/(kg·d)]. After continously intragastric administration with metfomrin for 42 days and GnRHa twice,the morphological changes of ectopic endometrium tissue were observed,and immunohistochemical study and Western blot were administered to detect expression of VEGF and MMP9. Results Four groups with treatment consistently decreased the volume of endometriotic lesions (P<0.05).In the immunohistochemical study, middle and low dose metfomrin group and GnRHa significantly decreased the expression of VEGF(P<0.05),and all dose metformin and GnRHa reduced the expression of MMP-9 significantly (P<0.05).In the Western-Blot, middle dose metformin decreased VEGF expression significantly (P<0.05), as well as middle and high dose metformin reduced MMP-9 significantly (P<0.05). Conclusion Metformin can inhibit the growth of endometriotic lesion and maybe a new therapy of endometriosis.
keywords:Endometriosis  Metformin  Vascular endothelial growth factor(VEGF)  Matrix metalloproteinase-9(MMP-9)
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