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-东南大学学报医学版

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

单位：东南大学,临床医学院,江苏,南京,210009

关键词：慢性移植物抗宿主病狼疮肾炎基质金属蛋白酶-9 组织金属蛋白酶抑制剂-1 小鼠

分类号：R-33, R593.242

出版年·卷·期（页码）：2007·26·第三期（189-193）

摘要：

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24 h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 24h 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.

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