氟伐他汀对慢性移植物抗宿主病狼疮样肾炎小鼠肾组织MMP-9／TIMP-1表达的影响  

Effects of fluvastatin on expression of MMP-9/TIMP-1 in renal tissue of murine chronic graft-versus-host disease lupus nephritis

作　　者：刘莉[1] 冯曹波[1] 王美美[2] 苗振春[1] 周俊[1] 

机构地区：[1]上海长海医院老年病科,上海200433 [2]东南大学附属中大医院风湿科,江苏南京210009

出　　处：《中国新药与临床杂志》2008年第12期881-885,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：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。AIM To determine the intervention of fluvastatin on improvement of the expressions of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in renal tissue of murine chronic graft-versus-host disease （cGVHD） lupus nephritis and evaluate the protective effects of fluvastatin. METHODS Eighteen female age-matched （C57BL/6J × DBA/2） F1 murine were randomly divided into three groups （n = 6） ： control group, model group （treated with intragastric infusion of equal volume of saline） and treated group （treated with fiuvastatin 0.22 mg intragastric infusion, individually）. The levels of urinary protein were measured in the 24-h urine collections using the blure T protein assay as a marker of renal damage.Immunohistochemistry and reverse transcription-polymerase chain reaction （RT-PCR） were taken to observe the expressions of MMP-9, TIMP-1 in renal tissue. Gelatin zymography was employed for MMP-9 activity examination. RESULTS Comparing with the control group, urinary protein excretion increased significantly in the treated group with markedly intense staining of MMP-9, TIMP-1 mainly in tubular epithelial cells and wall of vessels and the level of glomerular MMP-9 staining with positive correlation the level of total glomerular cell proliferation. In comparison with model group, treated group displayed instinctively the upregulating ratio of MMP-9/TIMP-1 and increase of MMP-9 activity; and together with less proteinuria than untreated murine. The rates of MMP-9/TIMP-1 and gelatinolytic activities of MMP-9 in treated-group decreased significantly. CONCLUSION The renal protection effect of fluvastatin may probably be achieved by decrease of MMP-9, TIMP-1 expression and MMP-9 activity and improvement of MMP-9/TIMP-1 imbalance.

关 键 词：移植物抗宿主病 狼疮肾炎 氟伐他汀 基质金属蛋白酶9 金属蛋白酶1组织抑制剂 

分 类 号：R972.6[医药卫生—药品]