Megsin基因转染对糖尿病小鼠肾脏炎症反应的影响及其机制研究

目的观察megsin基因转染对糖尿病小鼠肾组织单核细胞趋化蛋白-1(MCP-1)及细胞间黏附分子-1(ICAM-1)表达的影响,探讨megsin在糖尿病肾病发病机制中的作用。方法制备糖尿病小鼠模型,成模后随机选取10只作为糖尿病组(B组),剩余30只每周1次经尾静脉分别注射空质粒(C组),megsin表达质粒(D组),并设立正常对照组(A组)。实验共4周,于第4周末收集各组小鼠肾组织标本,分别应用Western blot和免疫组织化学染色测定肾组织中megsin、MCP-1、ICAM-1的表达;应用电镜观察肾小球超微结构的改变。结果糖尿病小鼠肾组织megsin、MCP-1及ICAM-1表达增强,基底膜普遍增厚,系膜区基质增多,上皮细胞足突融合;megsin基因转染后上述变化趋势更加显著。结论 megsin可上调MCP-1及ICAM-1表达,促进系膜细胞增殖及系膜外基质积聚,是加速肾小球硬化的可能机制之一。

Effects of megsin gene transfection on inflammation in diabetic mouse kidney and its mechanism

To observe the effects of megsin gene transfection on the expression of monocyte chemoattractant protein-1(MCP-1) and intercellular adhesion molecule-1(ICAM-1),and investigate the role of megsin in the pathogenesis of diabetic nephropathy,we established a model of diabetic mouse.Randomly selected 10 mice as the diabetic group(group B).The remaining 30 mice were respectively injected pCMV·SPORT6.1(group C),Megsin-pCMV·SPORT6.1(group D) via tail vein once a week,and the normal control group was established(group A).All animals were sacrificed at week 4 and kidney tissues were harvested.The expression levels of megsin,MCP-1,and ICAM-1 were detected by immunohistochemistry and Western blot.Electron microscopy was used to observe the pathological changes.In diabetic mouse kidney,we observed the increased expression of megsin,MCP-1,and ICAM-1,irregular thickening of glomerular basement membrane,mesangial expansion,and fusion of foot processes.The above changes were more significant after megsin gene transfection.Our results suggested that megsin gene can up-regulate the expression of MCP-1 and ICAM-1,induce mesangial cell proliferation and mesangial extracellular matrix accumulation,which is probably one of the mechanisms of accelerating glomerulosclerosis.