摘要
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)、 型胶原 ( C- )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- 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 .0 5 ) ,而 TGF- β1和 C- 则均较对照组明显上升 ( P<0 .0 5 ) ,且 MMP- 2与 TGF- β1、C- 均呈负相关 ( r=- 0 .4 5、- 0 .6 9,P<0 .0 5 )。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 .0 5 )。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- 降解减少 ,可能是引起细胞外基质积聚的原因之一。
Objective: To investigate the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9(MMP-9), transforming growth factor β 1(TGF-β 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-β 1 and C-Ⅳ were studied by immunohistochemistry. The results were analyzed by imaging quantitative analysis technique. Results: 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-β 1 and C-Ⅳ in the glomeluri of diabetic rats was significantly stronger than that of the controls ( P <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-β 1 and in turns promote the accumulation of C-Ⅳ.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2004年第3期245-249,共5页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省自然科学基金资助项目( 30 0 5 0 6 )
浙江省科技厅基金资助项目 ( 2 0 0 3C330 0 5 )
