Abstract
目的 研究基质金属蛋白酶-9(MMP-9)在糖基化终末产物(AGEs)所致血-视网膜屏障损害中的作用,评估米诺环素对AGEs所致血-视网膜屏障损害的治疗作用.方法 36只SD大鼠用随机数字表法分为牛血清白蛋白(BSA)组、AGEs-BSA组和AGEs-BSA+米诺环素组.BSA组和AGEs-BSA组分别自尾静脉注入BSA和AGEs-BSA,每日1次,每次40mg/kg,AGEs-BSA+米诺环素组在每日注射AGEs-BSA的同时隔日腹腔注射米诺环素45mg/kg.14d后,每组取6只大鼠用伊文思蓝(EB)法观察并比较各组视网膜血管的通透性,其余大鼠处死后,采用RT-PCR及Western blot法观察视网膜MMP-9的表达.结果 AGEs-BSA组MMP-9 mRNA和蛋白水平均较BSA组升高,差异有统计学意义(P＜0.01),同时,视网膜微血管渗透性也显著升高(P＜0.01).而在AGEs-BSA+米诺环素组大鼠视网膜基因和蛋白水平的MMP-9均被抑制(P＜0.01),同时视网膜微血管渗漏被部分逆转(P＜0.01).视网膜微血管的渗透性与MMP-9蛋白的表达呈正相关(r=0.891,P=0.000).结论 AGEs所致的视网膜微血管渗漏与MMP-9的高表达有密切关系,AGEs的作用至少部分是通过MMP-9实现的.米诺环素能部分逆转AGEs-MMP-9途径所致的血管渗漏。
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