基质金属蛋白酶-9/组织金属蛋白酶抑制剂-1在cGVHD狼疮样肾炎小鼠肾组织中的失衡

Imbalance between MMP-9 and TIMP-1 in kidney tissue of murine with chronic graft-versus-host disease lupus nephritis

目的:观察慢性移植物抗宿主病(cGVHD)狼疮样肾炎模型小鼠肾组织中基质金属蛋白酶-9(MMP-9)及组织金属蛋白酶抑制剂-1(TIMP-1)的表达及其意义。方法:12只B6D2F1代杂交鼠随机分为模型组和对照组,每组6只。双缩脲法测定24h尿蛋白量,免疫组织化学染色法及RT-PCR法观察肾组织中MMP-9、TIMP-1表达,明胶酶谱法检测MMP-9活性。比较两组的检测结果。结果:与对照组比较,模型组小鼠24 h尿蛋白量、MMP-9、TIMP-1蛋白及mRNA表达均明显升高(P<0.01),MMP-9/TIMP-1之值增加(P<0.01),MMP-9活性增强且其表达与增生的细胞数呈正相关(r=0.635,P=0.005)。结论:MMP-9/TIMP-1失衡是引起cGVHD狼疮样肾炎小鼠发病的机制之一。

Objective To explore expressions and significance of MMP-9 and TIMP- 1 in kidney tissue of murine with chronic graft-versus-host disease lupus nephritis. Methods The mice were randomly divided into model group and control group. The mouse urinary protein in 24 h was measured using the blure T. Immunohistochemistry and RT-PCR was used to observe the expression of MMP-9 ,TIMP-1 in kidney tissues. Gelatin zymography was used to perform MMP- 9 activity examination. Results Urinary protein excretion was increased significantly in the model group compared with the control group （P 〈 0.01 ）. Compared with control group ,the model group was found to has markedly intense staining of MMP-9, TIMP-1 mainly in tubular epithelial cells and walls of vessels （P 〈 0.01 ）. MMP-9 staining, which was almost negative in normal glomeruli, was increased mainly in the glomerular cells of model group. The level of glomerular MMP- 9 staining correlated significantly with the level of total glomerular cell proliferation （r = 0.635, P = 0.005 ）. Model group displayed instinctively upregulated gene expressions of MMP-9 ,TIMP-1 and increased MMP-9 activity. MMP-9/TIMP-1 up-regulation had been shown in mice of model group. Conclusion The unbalanced MMP/TIMP- 1 ratio plays a key role in the pathogenesis of murine lupus nephritis.