重组人肝再生增强因子对5/6肾切除大鼠肾组织MMP-9、 TIMP-1及Collgen-Ⅳ表达的影响

摘要

目的 探讨重组人肝再生增强因子(rhALR)是否可以通过影响基质金属蛋白酶9(MMP-9)、基质金属蛋白酶组织抑制因子1( TIMP-1)及Ⅳ型胶原(Collgen-Ⅳ)的表达,来延缓肾小球硬化.方法 雄性SD大鼠分为假手术组、对照组及rhALR组,以rhALR对5/6肾切除所致慢性肾衰竭大鼠进行干预.结果 与假手术组比较,对照组肾小球硬化指数增大,Collgen-Ⅳ、TIMP-1表达增加,MMP-9表达减少(P均＜0.05)；外源性给予rhALR能降低TIMP-1表达,增加MMP-9表达,减轻Collgen-Ⅳ的沉积,改善肾小球硬化(P均＜0.05).结论 rhALR可通过上调MMP-9/TIMP-1比例减少Collgen-Ⅳ积聚而改善肾小球硬化,保护残肾功能.%Objective To investigate the effects of rhALR on MMP-9, Collgen-Ⅳ and TIMP-1 with 5/6 nephrectomy rats. Methods Sixty healthy male SD rats were randomly divided into three groups; sham operation group (SO, n =20), CRF model group without treatment (C, n = 20) and CRF model group treated with rhALR (rhALR, n=20). Results Compared with group SO,the group C had a significantly higher glomerular sclerosis index and high level expression of Coll-gen-Ⅳ and TIMP-1, while the expression of MMP-9 was markedly decreased (P <0.05 ). The group dealt with rhALR had a down-regulating of expression of TIMP-1 and up-regulating of expression of MMP-9 compared with group C ( P < 0.05). Conclusions The rhALR acts as a factor contributing to decrease accumulation of Collgen-Ⅳ as well as protect the kidney against glomerular sclerosis by the up-regulating of expression of MMP-9 and the down-regulating of expression of TIMP-1 in renal tissues.