天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (3): 322-326.doi: 10.11958/59086

• 实验研究 • 上一篇    下一篇

福辛普利联合非诺贝特对糖尿病小鼠视网膜病变干预作用的研究

旷劲松 1， 赵玉蓉 1， 赵玉岩 2， 李若溪 1△， 辛彩虹   

  1. 1 沈阳市第四人民医院内分泌科（邮编 110032）；2沈阳， 中国医科大学附属第一医院内分泌科
  • 收稿日期:2015-06-15 修回日期:2015-11-25 出版日期:2016-03-15 发布日期:2016-03-15
  • 通讯作者: 李若溪 E-mail:xincaihong811221@163.com
  • 作者简介:旷劲松（1965）， 女， 博士研究生， 主任医师， 教授， 硕士生导师， 主要从事糖尿病并发症相关研究
  • 基金资助:
    国家自然科学基金资助项目（81470998）；辽宁省科学计划项目基金（2011225014）；沈阳市科技计划项目基金（F11-262-9-25）

The studying of Fosinopril combined with Fenofibrate on the preventing of Diabetic retinopathy in diabetic mice

KUANG Jinsong1, ZHAO Yurong1, ZHAO Yuyan2, Li Ruoxi1△, Xin Caihong1   

  1. 1 Department of Endocrinology, The Fourth People′s Hospital of Shenyang, Shenyang 110032, China; 2 Department of Endocrinology,The First Hospital of China Medical University
  • Received:2015-06-15 Revised:2015-11-25 Published:2016-03-15 Online:2016-03-15
  • Contact: Li Ruoxi E-mail:xincaihong811221@163.com

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摘要： 目的 研究福辛普利（Fosinopril）联合非诺贝特（Fenofibrate）对糖尿病小鼠视网膜细胞凋亡的影响及相关基因的表达和视网膜组织中血管内皮生长因子（vascular endothelial growth factor，VEGF）、氧化相关物质的影响，以明确其抑制糖尿病视网膜病变（diabetic retinopathy，DR）的作用机制。方法 选取清洁级性成熟ICR小鼠150只，随机分为5组（每组30只）：A组（假造模组，普通饲料喂养并给予相同体积的生理盐水）、B组（模型组，高脂饲料喂养4 w后给予腹腔注射链脲佐菌素（streptozotocin，STZ），给予相同体积生理盐水灌胃8 w）、C组（福辛普利对抗组，高脂饲料喂养4 w后给予腹腔注射链脲佐菌素，给予福辛普利干预8 w）、D组（非诺贝特对抗组，高脂饲料喂养4 w后给予腹腔注射链脲佐菌素，给予非诺贝特干预8 w）、E组（福辛普利+非诺贝特联合对抗组，高脂饲料喂养4 w后给予腹腔注射链脲佐菌素，给予福辛普利+非诺贝特干预8 w），0w和8w时测血糖BG，处死小鼠取眼球制备视网膜组织匀浆取上清检测谷光甘肽过氧化物酶（Glutathione peroxidase，GSH-PX）、超氧化物歧化酶（Superioxide dismutase，SOD）、活性氧类物质（Reactive oxygen species，ROS）、丙二醛（Malondialdehyde，MDA）、VEGF浓度，用RT-PCR法检测视网膜Bax与Bcl-2基因mRNA水平的表达，并用Tunel染色法检测视网膜细胞凋亡情况。结果B、C、D、E组小鼠用药前后血糖无差别(p>0.05); 均较A组明显升高(p<0.05);A组小鼠视网膜组织GSH-PX、SOD活性值及Bcl-2基因mRNA水平表达均高于其他四组（P＜0.05），而ROS、MDA、VEGF、Bax基因mRNA水平表达与Tunel指数均低于B、C、D组（P＜0.05）；B组小鼠GSH-PX、SOD活性值及Bcl-2基因mRNA水平表达均低于其他四组（P＜0.05），而ROS、MDA、VEGF、Bax基因mRNA水平表达与Tunel指数均高于其他四组（P＜0.05）；E组小鼠GSH-PX、SOD活性值及Bcl-2基因mRNA水平表达均高于C、D组（P＜0.05），而ROS、MDA、VEGF、Bax基因mRNA水平表达与Tunel指数均低于C、D组（P＜0.05）；D组小鼠GSH-PX、SOD活性及Bcl-2基因mRNA水平表达均高于C组（P＜0.05），而ROS、MDA、Bax基因mRNA水平表达与Tunel指数均低于C组（P＜0.05）；C组小鼠VEGF浓度值低于D组（P＜0.05）。结论 福辛普利及非诺贝特均能改善DR，通过抑制凋亡与抗氧化对视网膜起到一定的保护作用，但两药联合应用效果更佳。

关键词: 糖尿病视网膜病变, 糖尿病并发症, 氧化性应激, 细胞凋亡, 疾病模型, 动物, 福辛普利, 非诺贝特, 血管内皮生长因子

Abstract: 【Objective】 Studying the mechanism of the Fosinopril combined with Fenofibrate on the preventing of diabetic retinopathy and detecting the apoptosis and apoptosis reletive gene in the level of mRNA in the retinopathsis tissue ,the VEGF oxidizing material in the retina.【Method】 150 viripotent ICR mice(100 male mice,50 female mice) were randomly divided into five groups,every group included 30 mice. A group(Sham group, common forage given,Sodium Chloride injected),B group(Model group,exposure to high-fat diet for 4 weeks,mice were injected intraperitoneally with STZ,then lavaged with Sodium Chloride for 8 weeks),C group(Fosinopril preventing group, exposure to high-fat diet for 4 weeks,mice were injected intraperitoneally with STZ,then lavaged with fosinopril for 8 weeks),D group(Fenofibrate preventing group, exposure to high-fat diet for 4 weeks,mice were injected intraperitoneally with STZ,then lavaged with fenofibrate for 8 weeks),E group(Fosinopril combined with Fenofibrate preventing group,exposure to high-fat diet for 4 weeks,mice were injected intraperitoneally with STZ,then lavaged with fosinopril combined with fenofibrate for 8 weeks), Drawing the retina to detecing the activity of GSH-PX,SOD,ROS and the concentration of MDA and VEGF,then the mice were euthanized then detected the gene of Bax and Bcl-2 in the level of mRNA through the RT-PCR and detected the apoptosis of retinal cells through the Tunel staining method in the eyes.【Results】The BG of A group is lower than that of B,C,D ,E group(p<0.05)and which of B,C,D,E group are similar(p>0.05);A group expressed more Bcl-2 in the level of mRNA and the activity of GSH-PX,SOD were higher than other four groups(P＜0.05),but the concentration of ROS,MDA,VEGF,the expression of Bax in the level of mRNA and the Tunel index were lower than the B ,C, D groups(P＜0.05);B group expressed less Bcl-2 in the level of mRNA and the activity of GSH-PX,SOD were lower than other four groups(P＜0.05),but the concentration of ROS,MDA,VEGF,the expression of Bax in the level of mRNA and the Tunel index were higher than other four groups(P＜0.05);E group expressed less Bcl-2 in the level of mRNA and the activity of GSH-PX,SOD were lower than other C,D groups(P＜0.05),but the concentration of ROS,MDA,,the expression of Bax in the level of mRNA and the Tunel index were higher than C,D groups(P＜0.05);D group expressed more Bcl-2 in the level of mRNA and the activity of GSH-PX,SOD were higher than C group(P＜0.05),but the concentration of ROS,MDA,the expression of Bax in the level of mRNA and the Tunel index were lower than C group(P＜0.05);The concentration of VEGF in the Cgroup was lower than D group(P＜0.05).【Conclusions】 Fosinopril and Fenofibrate can improve the DR through inhibit the apoptosis and oxidation can conservate the retina,but Fosinopril combinated with Fenofibrate can get the better effect.

Key words: diabetic retinopathy, diabetes complications, oxidative stress, apoptosis, disease models, animal, Fosinopril, Fenofibrate, vascular endothelial growth factor