CAJ | 학술논문

目的：观察Egr－1基因转染对糖尿病小鼠肾组织肿瘤坏死因子α（ TNF－α）及细胞间黏附分子1（ ICAM－1）表达的影响，探讨Egr－1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，剩余40只每周1次经尾静脉分别注射空质粒、Egr－1表达质粒和Egr－1 siRNA质粒，并设立正常对照组。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Egr－1、TNF－α和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Egr－1、TNF－α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；Egr－1基因转染后上述变化趋势更加显著。siRNA质粒转染组上述变化较糖尿病组明显减轻。结论：Egr－1可上调TNF－α及ICAM－1表达，促进系膜细胞增殖及系膜外基质积聚，可能是加速肾小球硬化的可能机制之一。
목적：관찰Egr－1기인전염대당뇨병소서신조직종류배사인자α（ TNF－α）급세포간점부분자1（ ICAM－1）표체적영향，탐토Egr－1재당뇨병신병발병궤제중적작용。방법：제비당뇨병소서모형，성모후수궤선취10지작위당뇨병조，잉여40지매주1차경미정맥분별주사공질립、Egr－1표체질립화Egr－1 siRNA질립，병설립정상대조조。실험공4주，우제4주말수집각조소서신조직표본，분별응용western blot 화면역조직화학염색측정신조직중Egr－1、TNF－α화ICAM－1적표체；응용전경관찰신소구초미결구적개변。결과：당뇨병소서신조직Egr－1、TNF－α급ICAM－1표체증강，기저막보편증후，계막구기질증다，상피세포족돌융합；Egr－1기인전염후상술변화추세경가현저。siRNA질립전염조상술변화교당뇨병조명현감경。결론：Egr－1가상조TNF－α급ICAM－1표체，촉진계막세포증식급계막외기질적취，가능시가속신소구경화적가능궤제지일。
AIM:To observe the effects of Egr-1 gene transfection on the expression of tumor necrosis factor-α( TNF-α) and intercellular adhesion molecule-1 ( ICAM-1) , and to investigate the role of Egr-1 in the pathogenesis of dia-betic nephropathy .METHODS:The diabetic mouse model was established .Ten mice were randomly selected as the dia-betic group .The remaining 40 mice were injected with empty plasmid , Egr-1 expression plasmid or Egr-1 siRNA plasmid via the tail vein once a week.The normal control group was also set up .The animals were sacrificed at the end of the 4th week.The renal tissues were harvested .The expressions of Egr-1, TNF-αand ICAM-1 were detected by immunohisto-chemistry and Western blot .The pathological changes were observed under electron microscope .RESULTS: In diabetic mouse kidney, the expression of Egr-1, TNF-αand ICAM-1 was increased, and irregular thickening of glomerular basement membrane , mesangial expansion and fusion of foot were observed .The change trend was more significant in Egr-1 gene transfection group , and these changes in siRNA plasmid transfection group were obviously reduced compared with diabetes group.CONCLUSION:Egr-1 up-regulates the expression of TNF-αand ICAM-1, and induces mesangial cell proliferation and mesangial extracellular matrix accumulation , which is probably one of the mechanisms of accelerating glomerulosclerosis .