糖尿病大鼠肾组织中PKB与MMP-9及TIMP-1表达关系的研究

Strategy for Development of Pharmaceutical InformatricsTo Study the Relation of PKB and MMP-9 , TIMP-1 in the Pathogenesis of Diabetic Nephropathy Rats

目的观察蛋白激酶B（PKB）、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶抑制因子-1（TIMP-1）在糖尿捅大鼠肾组织甲的表达及相互关系，从而探讨PKB在糖尿病肾病（DN）发病机制中的作用。方法大鼠随机分为糖尿病（DM）组、正常对照（C）组、胰岛素治疗（A）组。检测肾组织中PKB、MMP-9、TIMP-1的表达。结果PKB阳性染色见于各组大鼠肾小管上皮细胞，但DM组大鼠肾组织中PKB阳性表达显著增加（P〈005）；DM组肾小管上皮细胞TIMP-1的阳性表达显著增加（P〈0．05）；DM组肾小管上皮细胞MMP-9阳性表达显著增加，但随着病程进展至8周后MMP-9的阳性表达呈逐渐减少的趋势。PKB与MMP-9的表达呈负相关，与TIMP-1的表达呈显著正相关。与MMP-9／TIMP-1比值呈显著负相关。结论PKB在DN大鼠肾组织高表达且与MMP-9和TIMP-1及MMP-9／TIMP-1比值变化有明显的相关性．推测在糖尿病大鼠肾组织中，PKB通过调控MMP一9及TIMP-1表达的变化，使得MMP-9／TIMP-1平衡紊乱，细胞外基质（ECM）降解受到抑制．从而促进了DN的发生。

Objective To observe the dynamic changes of protein kinase B expression in renal tissues of diabetic rats induced by streptozotocin（STZ）, and its relation ship with matrix metalloproteinases,tissue inhibitor of metalloproteinase,in order to elucidate the role of protein kinase B in the diabetic Nephropathy（DN） Kid fibrosis.Methods：Rats were randomly divided into control group, DMand insulin-treated groups.The protein expression of PKB, MMP-9,TIMP-1 were detected.Results PKB protein stainings was observed in renal tubules of DM rats.PKB and TIMP-1 were significantly Up-regulated in renal cortex of diabetic rats （P〈0.05）, But the expression MMP-9 were significantly down-regulated in DM rats.PKB is negative correlation with expression of MMP-9,positive crrelation with expression of TIMP-1 negative correlation with expression of MMP-9/TIMP-1. Conclusion The negative regulation of PKB to expression of MMP-9 promotes the occurrence and development of diabetic nephropathy Kid fibrosis. The changes in the expression of PKB of renal tubular epithelial cell in diabetic rats may be involved in the pathogenesis of diabetic nephropathy kid fibrosis.