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目的观察氟伐他汀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)、金属蛋白酶1组织抑制剂(TIMP-1)表达的干预作用,探讨氟伐他汀对肾脏的保护机制。方法B6D2F1代杂交鼠随机分为3组(均n=6):正常对照组、模型组和氟伐他汀组。制作狼疮样肾炎小鼠模型后,氟伐他汀组每只小鼠予氟伐他汀0.22 mg灌胃,模型组每只予等量生理盐水灌胃。双缩脲法测定24 h尿蛋白量;免疫组织化学染色法及逆转录-多聚酶链反应(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。结果与正常组相比,模型组小鼠24 h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,氟伐他汀组尿蛋白量、MMP-9、TIMP-1表达及比值均降低,MMP-9活性下降。结论氟伐他汀可能通过降低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。
Objective To investigate the effects of fluvastatin on the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in renal tissue of chronic graft-versus-host disease (cGVHD) The protective mechanism of fluvastatin on the kidneys. Methods B6D2F1 hybrid mice were randomly divided into 3 groups (all n = 6): normal control group, model group and fluvastatin group. After the mouse model of lupus-like nephritis was made, fluvastatin 0.22 mg was given to each mouse in the fluvastatin group, and the rats in the model group were given the same amount of normal saline. The urinary protein levels of 24 h were measured by the biuret method. The expressions of MMP-9 and TIMP-1 in renal tissues were detected by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) active. Results Compared with the normal group, the 24 h urinary protein, MMP-9, TIMP-1 expression and the ratio increased, the activity of MMP-9 increased, and positively correlated with the mesangial cell proliferation In the fluvastatin group, the expression of urinary protein, MMP-9 and TIMP-1 decreased and MMP-9 activity decreased. Conclusions Fluvastatin may play a protective role in kidney by reducing the expression of MMP-9, TIMP-1 and MMP-9 activity and improving the imbalance of MMP-9 / TIMP-1.