基础医学与临床 ›› 2016, Vol. 36 ›› Issue (12): 1687-1692.

• 研究论文 • 上一篇    下一篇

基质金属蛋白酶抑制剂-1减轻糖尿病小鼠视网膜损伤

丁熊,刘辉,王琳玲,王平   

  1. 三峡大学第二临床学院附属仁和医院
  • 收稿日期:2016-01-13 修回日期:2016-05-04 出版日期:2016-12-05 发布日期:2016-11-29
  • 通讯作者: 王平 E-mail:dayijingcheng2012@foxmail.com

Metalloproteinase inhibitor-1 reduced retinal injury in diabetic mice

  • Received:2016-01-13 Revised:2016-05-04 Online:2016-12-05 Published:2016-11-29

摘要: 目的 探讨基质金属蛋白酶抑制剂-1(TIMP-1)对糖尿病小鼠视网膜的保护作用及机制。方法 将96只6~8周龄C57bl小鼠随机分为对照组、糖尿病组和TIMP-1干预组(糖尿病造模后第1和2个月玻璃体腔注射5μL TIMP-1(1mg/L)各1次)。5个月后进行视网膜灌注铺片检测渗漏,Western blot和RT-qPCR分别检测基质金属蛋白酶9(MMP-9)、血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)和环氧合酶-2(COX-2)mRNA及蛋白表达,用生化法检测视网膜组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量。结果 对照组视网膜无渗漏,糖尿病组视网膜渗漏明显高于TIMP-1干预组(p<0.01)。糖尿病组视网膜MMP-9、VEGF、TNF-α、COX-2 mRNA与蛋白表达水平以及MDA含量均明显高于对照组(p<0.01),TIMP-1干预组则显著回降(p<0.01),但仍高于对照组(p<0.01);糖尿病组视网膜SOD、GSH-Px活性明显低于对照组(p<0.01),TIMP-1干预组则显著回升(p<0.01),但仍低于对照组(p<0.01)。结论 TIMP-1能够通过减少氧化应激与VEGF表达对糖尿病小鼠视网膜起保护作用。

关键词: 糖尿病视网膜病变, 基质金属蛋白酶抑制剂-1, 氧化应激

Abstract: Objective To investigate the protective effect and mechanism of matrix metalloproteinase inhibitor-1 (TIMP-1) against diabetic retinopathy in mice. Methods A total of 96 of 6-8 weeks old C57bl mice were randomly divided into 3 groups: control group, diabetic group and TIMP-1 group (mice were intravitreously injected with TIMP-1 5μl (1μg/ml) in the first and second months respectively after diabetes-induced). Retinal vascular leakages were investigated by retinal perfusion of evans blue after 5 months. The mRNA and protein expression levels of metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α) and epoxy synthase -2 (COX-2) were also analyzed by RT-qPCR and Western blot. And the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content in the retina tissue were also detected with bio-chemical method. Results There was no retinal leakage in control group, but diabetic group was significantly higher than TIMP-1 group (p<0.01). The mRNA and protein expression levels of MMP-9, VEGF, TNF-α, COX-2 and the MDA content in diabetic group were significantly higher than control group (p<0.01), while in TIMP-1 group they decreased (p<0.01) and also higher than control group (p<0.01). The SOD and GSH-Px activity in diabetic group were significantly lower than control group(p<0.01),while in TIMP-1group they increased (p<0.01) and also lower than control group (p<0.01). Conclusions TIMP-1 can protect the retina of diabetic mice by reducing the oxidative stress and the expression of VEGF.

Key words: diabetic retinopathy, matrix metalloproteinase inhibitor-1, oxidative stress

中图分类号: