摘要
建立慢性移植物抗宿主病(cGVHD)狼疮样小鼠模型,观察c-Jun氨基末端激酶(JNK)在狼疮样小鼠肾组织中的表达及氟伐他汀的干预作用。(C57BL/6J×DBA/2)F1代小鼠随机分为正常对照组、氟伐他汀高剂量组(10mg/kg)、低剂量组(5mg/kg)和模型组,16周后处死,采用双缩脲比色法观察各组小鼠24h尿蛋白量,免疫组织化学法定位检测JNK、p-JNK在肾组织的表达,RT-PCR法检测各组JNK mRNA表达及Western blotting半定量检测JNK、p-JNK蛋白表达。结果显示,模型组小鼠24h尿蛋白量、JNK mRNA及JNK、p-JNK蛋白表达较正常对照组均显著增加(P<0.01);氟伐他汀干预组较模型组上述指标均明显降低(P<0.01);高剂量组较低剂量组降低更明显(P<0.05)。JNK可能参与了狼疮肾炎病情进展,氟伐他汀可能通过影响JNK的表达从而延缓狼疮肾炎肾纤维化进程。
This study was aimed to detect the expression of c-Jun N-terminal kinase （JNK） in renal tissues of lupus nephritis （LN） mice with chronic graft-versus-host disease （cGVHD） and to investigate that LN could be intervened by fluvastatin at different doses through the inhibition of JNK expression.LN models with cGVHD in mice were established first,and then diseased mice were randomly divided into four groups：normal control,fluvastatin intervention at high-dose group （10 mg/kg）,fluvastatin intervention at low-dose group （5mg/kg） and models without treatment.After killing the mice sixteen weeks later,total urine protein of every mouse was determined by a Biuret colorimetric assay.The protein and mRNA levels of JNK and p-JNK in kidneys were measured by immunohistochemistry,Western blot and RT-PCR,respectively.Compared with normal control,otal urine protein,JNK and p-JNK expressions at both mRNA and protein levels were significantly increased in cGVHD group （P〈0.01）,but their expressions were suppressed by fluvastatin treatment （P〈0.01）.JNK may play an important role in the pathogenetic progress of LN in mice,and fluvastatin is able to prevent LN via inhibition of JNK expression in renal tissues in cGVHD mice.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2010年第2期180-185,共6页
Journal of China Pharmaceutical University
