氟伐他汀对慢性移植物抗宿主病狼疮性肾炎模型小鼠肾组织p38 MAPK表达的影响

Effects of fluvastatin on expression of p38 mitogen-activated protein kinase in renal tissue of chronic graft versus host disease lupus nephritis in mice

目的探讨氟伐他汀对慢性移植物抗宿主病（cGVHD）狼疮性肾炎模型小鼠肾组织中p38丝裂原活化蛋白激酶（p38MAPK）表达的干预作用。方法将（C57BIM6J×DBA／2）F1杂交小鼠随机分为模型组、低剂量氟伐他汀干预组（5mg·kg^-1·d^-1）、高剂量氟伐他汀干预组（10mg·kg^-1·d^-1）及正常对照组，氟伐他汀干预组小鼠每13氟伐他汀灌胃；双缩脲比色法测定24h尿蛋白量，免疫组化及Western印迹法检测p38MAPK、p-p038MAPK、TGF—β1蛋白定位及半定量表达，RT—PCR法检测p38MAPK、TGF-β1mRNA的表达。结果模型组小鼠24h尿蛋白量、p38MAPK、p—p38MAPK和TGF—β1蛋白及mRNA表达均明显高于正常对照组[（7．84±0．36）比（1.15±0．15）mg／24h、0．81±0．03比0．50±0．01、0．69±0．02比0．10±0．01、0．76±0．02比0．28±0．02及0．84±0．04比0．25±0．02、0．82±0．04比0．12±0．02，均P〈0．01]，与模型组相比，氟伐他汀干预组上述指标均降低（均P〈0．05），且高剂量组低于低剂量组（P〈0．05）。结论氟伐他汀可能通过影响p38MAPK信号通路延缓狼疮性肾炎肾脏纤维化进程。

Objective To explore the effects of fluvastatin on expression of p38 mitogen-activated protein kinase （p38MAPK） in renal tissue of chronic graft versus host disease （cGVHD） lupus nephritis in mice. Methods Mice were randomly divided into 4 groups of model, low-close fluvastatin intervention （5mg·kg^-1·d^-1）, high-dose fluvastatin intervention （10 mg·kg^-1·d^-1） and normal control. The 24 h total amount of urine protein was evaluated by biuret reaction colorimetric assay. And the protein and mRNA expression levels of p38MAPK, p-p38MAPK and TGF-β1 in renal tissue were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction （RT-PCR） respectively. Results Compared with the normal control group, 24 h total amount of urine protein, protein and mRNA expression levels of p38MAPK, p-p38MAPK and TGF-β1 increased significantly in the model group respectively （ （7. 84 ±0. 36） vs （1.15 ±0. 15） mg/24 h, 0. 81 ±0. 03 vs 0. 50 ±0. 01,0. 69 ±0. 02 vs 0. 10 ±0. 01, 0. 76 ±0. 02 vs 0. 28 ±0. 02, 0. 84 ±0.04 vs 0. 25 ±0. 02, 0. 82 ±0. 04 vs 0. 12 ±0. 02, all P 〈 0. 01 ）. Fluvastatin treatment suppressed markedly their increased expressions （P 〈0. 05 ）. And highdose fluvastatin treatment suppressed more significantly than low-dose group （ P 〈 0. 05 ）. Conclusion The renal protection effect of fluvastatin may be achieved by inhibiting the signal pathway of p38MAPK.