参地颗粒对系膜增生性肾小球肾炎大鼠血清和肾脏MMP-9/TIMP-1的影响

Effects of Shendi Granule on MMP-9/TIMP-1 in Serum and Kidney Tissue among Rats with Mesangial Proliferative Glomerulonephritis

目的探究参地颗粒治疗系膜增生性肾小球肾炎(mesangial proliferative glomerulonephritis,MsPGN)的机制。方法采用改良慢性血清病法复制MsPGN模型。将37只SD大鼠随机分为空白组(n=10)、模型组(n=8)、贝那普利组(n=9)和参地颗粒组(n=10)。常规生化法检测24h尿蛋白定量(24-hour urinary protein,24hUP),酶联免疫吸附法测定血清纤维连接蛋白(fibronectin,FN)、Ⅳ型胶原(collagen-Ⅳ,Col-Ⅳ)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)水平,光镜下观察肾脏组织病理学变化,采用免疫组织化学法检测大鼠肾组织MMP-9和TIMP-1蛋白表达水平。结果与模型组比较,参地颗粒组和贝那普利组大鼠24hUP水平,血清FN、Col-Ⅳ水平,以及肾小球基质相对面积显著降低(P<0.05);参地颗粒组血清和肾组织MMP-9水平显著升高(P<0.05),TIMP-1水平显著降低(P<0.05),血清MMP-9/TIMP-1比值显著升高(P<0.05)。给药4周和8周后,参地颗粒组24hUP均显著低于贝那普利组(P<0.05),血清和肾组织MMP-9/TIMP-1比值显著高于贝那普利组(P<0.05)。结论参地颗粒可以降低MsPGN大鼠24hUP,降低肾脏细胞外基质含量,其机制可能与上调体内MMP-9水平、下调TIMP-1水平及升高MMP-9/TIMP-1比值有关。

Objective To investigate the action mechanism of Shendi Granule in the treatment of mesangial proliferative glomerulonephritis （MsPGN）.Methods A rat model of MsPGN was induced by modified chronic serum sickness method.Thirty-seven Sprague-Dawley rats were randomly divided into blank group （n=10）,model group （n=8）,benazepril group （n=9）,and Shendi Granule group （n=10）.The 24-hour urinary protein （24hUP） excretion was quantified by conventional biochemical method.Serum levels of fibronectin （FN）,collagen V （Col Ⅳ）,matrix metalloproteinase 9 （MMP 9）,and tissue inhibitor of metalloproteinase-1 （TIMP-1） were determined by enzyme-linked immunosorbent assay.The histopathological changes in the kidney were observed under a light microscope.The protein expression of MMP-9 and TIMP-1 in kidney tissue was measured by immunohistochemistry.Results Compared with the model group,the Shendi Granule group and benazepril group had significantly reduced 24hUP excretion,serum FN and Col Ⅳ levels,and relative area of glomerular extracellular matrix （P＜0.05）,and the Shendi Granule group had significantly increased MMP-9 levels in serum and kidney tissue （P＜0.05）,a significandy reduced TIMP-1 level （P＜0.05）,and a significantly increased MMP-9/TIMP-1 ratio （P＜0.05）.After 4 and 8 weeks of treatment,the Shendi Granule group had a significantly lower 24hUP excretion （P＜0.05） and a significantly higher MMP-9/TIMP-1 ratio in serum and kidney tissue （P＜0.05）,as compared with the benazepril group.Conclusion Shendi Granule can reduce 24hUP excretion and glomerular extracellular matrix content in rats with MsPGN,possibly by upregulating MMP-9 level and downregulating TIMP-1 level.