肾络宁对IgA肾病大鼠肾间质细胞外基质代谢的影响

Effect of Shen Luo-ning on Extracellular Matrix Metabolism of Kidney Interstitial Tissue in IgA Nephrosis Rats

关键词:  肾络宁  IgA肾病  间质  细胞外基质

Key words:  Shen Luo-Ning  IgA Nephrosis  interstitial  extracellular matrix

摘要:

[目的]通过复制免疫球蛋白A肾病(IgAN)大鼠模型,探讨肾络宁对IgAN大鼠肾间质细胞外基质(ECM)代谢的影响。[方法]口服并定时尾静脉注射牛血清白蛋白,复合葡萄球菌肠毒素感染的方法复制IgAN模型,同时给予肾络宁治疗,利用原位分子杂交和免疫组织化学的方法,结合计算机病理图像分析,观察肾络宁对IgAN大鼠肾间质Ⅲ型胶原(ColⅢ)、纤溶酶原激活物抑制剂1(PAI-1)、基质金属蛋白酶1(MMP-1)及组织型基质金属蛋白酶抑制剂1(TIMP-1)基因及蛋白表达的影响。[结果]1)肾络宁组肾间质ColⅢ蛋白及PAI-1、TIMP-1mRNA表达与模型组相比明显降低(P<0.01或0.05)。2)肾络宁组肾间质MMP-1mRNA表达与模型组相比显著升高(P<0.01)。[结论]肾络宁能降低IgAN模型大鼠肾间质ColⅢ蛋白的表达,下调PAI-1、TIMP-1mRNA的表达,上调MMP-1mRNA的表达,从而发挥调节ECM代谢的作用。

Abstract:

[Objective] To investigate the effect of Shen luo-ning (calming kidney collateral, SLN) on the extracellular matrix metabolism of kidney interstitial tissue in rats with IgA Nephrosis(IgAN).[Methods] IgAN in rats was established by taking bovine serum albumin(BSA) orally first and then intravenously via tail vein at fixed hour, combined with staphylococcus enterotoxin B (SEB) infection. SLN was given as a treatment. Using in situ hybridization(ISH) immunohistochemistry and computer image analysis the effects of SLN on the expression of transforming growth factor β1 (TGFβ1), collagen type Ⅲ(Col-Ⅲ), inhibitor of plasminogen activator (PAI-1), matrix metalloproteases-1 (MMP-1) and the gene and protein expression of tissue inhibitors of matrix metalloproteases-1 (TIMP-1) in kidney interstitial of IgAN rats were determined.[Results] In kidney interstitial, the mRNA expression of TGFβ1, Col-Ⅲ, PAI-1, TIMP-1 of model group was higher than that of normal group(P<0.01 or P<0.05). In the treatment group, the expression of MMP-1mRNA was higher than model group(P<0.01).[Conclusions] SLN can reduce kidney interstitial pathologic injury in rats woth IgAN . The above-mentioned actions may be related with that SLN can down-regulate the expression of TGFβ1, Col-Ⅲ, PAI-1, TIMP-1 and up-regulate that of MMP-1. This may be the mechanisms of SLN preventing and curing kidney interstitial injury in rats with IgAN.