糖尿病大鼠肾小球基质金属蛋白酶2和9的表达

目的:对糖尿病大鼠模型的肾组织中的基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、Ⅳ型胶原(C-Ⅳ)和转化生长因子β1(TGF-β1)的表达进行定量和定位研究,探讨糖尿病肾病的发病机理.方法:SD大鼠腹腔注射链脲佐菌素(70 mg/kg)诱发糖尿病,肾标本行常规病理检查,用MMP-2 、MMP-9、C-Ⅳ单克隆抗体及TGF-β1多克隆抗体标记进行免疫组织化学染色、图象分析仪分析.结果:正常大鼠MMP-2、MMP-9主要表达在肾小球系膜细胞、内皮细胞、包曼氏囊壁层上皮细胞、肾小管上皮细胞,偶见浸润的巨噬细胞和中性粒细胞表达.造模后2、4、8周时糖尿病组大鼠肾小球MMP-2较对照组明显下降(P<0.05),而TGF-β1和C-Ⅳ则均较对照组明显上升(P<0.05),且MMP-2与TGF-β1、C-Ⅳ均呈负相关(r=-0.45、-0.69, P<0.05).肾小球MMP-9在三组各时点均未显示显著性差异,糖尿病组肾小球MMP-9较正常对照组似有升高趋势,但无统计学差异(P>0.05).结论:糖尿病时伴有肾小球MMP-2表达水平的下降可能与TGF-β1水平的升高有关,MMP-2的减少导致C-Ⅳ降解减少,可能是引起细胞外基质积聚的原因之一.

Expression of matrix metalloproteinase -2 and -9 in kidney of diabetic rats

OBJECTIVE: To investigate the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9(MMP-9), transforming growth factor beta(1)(TGF-beta(1)) and IV-collagen (C-IV) in kidneys of diabetic rats. METHODS: Rat diabetic model was induced by streptozotocin (70 mg/kg), and kidneys were examined pathologically and the expressions of MMP- 2, MMP-9, TGF-beta(1) and C-IV were studied by immunohistochemistry. The results were analyzed by imaging quantitative analysis technique. RESULT: Immunoreactive MMP-2 and MMP-9 were mainly expressed in the mesangial cells, endothelial cells, parietal layer of Bowman's capsule and tubular cells. The expression of MMP-2 was significantly weaker in the glomeluri of diabetic rats than that of the control animals (P<0.05), while the expression of TGF-beta(1) and C-IV in the glomeluri of diabetic rats was significantly stronger than that of the controls (P%lt;0.05). The expression of MMP-9 didn't show significant different in glomeluri of the two groups (P>0.05). CONCLUSION: Expression of MMP-2 in glomeluri is decreased in diabetic rats, which may be related to the increased TGF-beta(1) and in turns promote the accumulation of C-IV.