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目的:观察缬沙坦对慢性移植物抗宿主病(cGVHD)狼疮样肾炎小鼠肾组织中基质金属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)表达的干预作用,探讨缬沙坦对肾脏的保护机制。方法:18只B6D2F1代杂交鼠,随机分为狼疮肾炎模型组(12只)和对照组(6只)。随机将狼疮肾炎模型组分为模型组(6只)和缬沙坦组(6只)。双缩脲法测定24h尿蛋白量;免疫组织化学染色法及反转录-聚合酶链反应(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。结果:与对照组相比,狼疮肾炎模型组小鼠24h尿蛋白量、MMP-9、TIMP-1表达及比值均增加,MMP-9活性增强,且与系膜细胞增殖呈正相关;与模型组相比,缬沙坦组尿蛋白量、MMP-9、TIMP-1表达及比值均降低,MMP-9活性下降。结论:缬沙坦降低MMP-9、TIMP-1表达及MMP-9活性,改善MMP-9/TIMP-1失衡,从而发挥肾脏保护作用。
AIM: To observe the effects of valsartan on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the kidney of chronic graft versus host disease (cGVHD) Role of valsartan on kidney protection mechanism. Methods: Eighteen B6D2F1 generation crossbred rats were randomly divided into lupus nephritis model group (n = 12) and control group (n = 6). Lupus nephritis model group was randomly divided into model group (6) and valsartan group (6). The amount of urinary protein in 24h was measured by the biuret method. The expression of MMP-9 and TIMP-1 in renal tissue was detected by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) 9 activity. Results: Compared with the control group, the expression of urinary protein, MMP-9 and TIMP-1 in lupus nephritis model group increased and the ratio of MMP-9 and TIMP-1 increased in the lupus nephritis model group and increased positively with the proliferation of mesangial cells. Compared with valsartan group, urinary protein, MMP-9, TIMP-1 expression and ratio decreased, MMP-9 activity decreased. Conclusion: Valsartan can decrease the expression of MMP-9, TIMP-1 and the activity of MMP-9, and improve the imbalance of MMP-9 / TIMP-1.