吡格列酮对糖尿病大鼠氧化应激和肾组织基质积聚的影响

目的研究吡格列酮对链脲佐菌素(STZ)诱导的糖尿病大鼠氧化应激及肾组织细胞外基质蛋白积聚的影响。方法将45只大鼠随机分为3组:正常对照组(NC组),糖尿病对照组(DM组),糖尿病吡格列酮治疗组(DP组)。DP组给予吡格列酮20mg.kg-1.d-1灌胃。8周后观察大鼠肾指数(KI)、尿微量清蛋白(MAU)、肾组织丙二醛(MAD)、过氧化氢酶(CAT)、铜锌超氧化物歧化酶(Cu,Zn-SOD)等,光镜及超微电镜观察肾脏病理形态学改变,免疫组化法观察肾组织Ⅳ型胶原表达。结果 DM组大鼠KI、MAU、肾组织MAD水平显著高于NC组,并出现典型糖尿病肾病(DN)病理学损害,而DP组KI、MAU、MAD水平明显下降,差异有统计学意义(P<0.01);DM组大鼠肾组织CAT、Cu-ZnSOD水平较NC组降低(P<0.01),DP组CAT、Cu-ZnSOD显著上升(P<0.01)。DM组大鼠肾组织Ⅳ型胶原表达明显增多,DP组表达显著降低(P<0.01)。结论吡格列酮可通过抑制氧化应激反应、减轻细胞外基质积聚,对DN起保护作用。

Effect of pioglitazone on oxidative stress and accumulation of matrix in diabetic rats

Objective To investigate the effect of pioglitazone on oxidative stress and accumulation of matrix in diabetic rats.Methods All rats were randomized into 3 groups:normal control rats(group NC),diabetic rats(group DM),diabetic rats treated with pioglitazone(group DP).After 8 weeks of treatment,the kidney index,microalbuminuria,malondialdehyde,catalase,Cu,Zn superoxide dismutase in nephridial tissue were measured by chromatometry,the pathologic change of kidney was measured.Furthermore,collagen-Ⅳexpression in kidneny was observed by immunohistochemistry.Results The kidney index,microalbuminuria,MDA and the expression Col-Ⅳ in group DM were higher significantly than those in the group NC and group DP(P<0.01),Morever,CAT in the group DM was significantly lower than that in the other two groups(P<0.01).Conclusion Pioglitazone improves diabetic nephropathy through downregulating the expression of TGF-β1 and upregulating MMP-9 in diabetic rats.