基础医学与临床 ›› 2010, Vol. 30 ›› Issue (12): 1293-1298.

• 研究论文 • 上一篇    下一篇

辛伐他汀降低脂质肾损害大鼠肾组织中骨调素表达

陈利群1,甘华2,吕智美2   

  1. 1. 重庆医科大学附属第一医院2. 重庆医科大学附属第一医院肾内科
  • 收稿日期:2009-10-27 修回日期:2010-05-04 出版日期:2010-12-05 发布日期:2010-12-05
  • 通讯作者: 陈利群

Simvastatin decreased the osteopontin expression in lipid-induced rats renal injury

CHEN Li-qun ,GAN Hua ,LV Zhi-mei   

  1. The first Affiliate Hospital,Chongqing Medical Sciences University
  • Received:2009-10-27 Revised:2010-05-04 Online:2010-12-05 Published:2010-12-05
  • Contact: CHEN Li-qun

摘要: 目的 观察高脂血症肾损害大鼠肾组织中骨调素(OPN)和单核细胞趋化蛋白1 (MCP-1)表达变化及辛伐他汀对其表达的影响。方法 将雄性wistar大鼠随机分为对照组,高脂组,辛伐他汀治疗组,每组10只。观察12周。实验监测尿蛋白量、血脂、肾功能及肾组织病理学改变;免疫组化技术检测肾组织MCP-1表达,用RT-PCR、免疫印迹检测OPN mRNA和蛋白表达。 结果 实验结束时,高脂模型组及辛伐他汀组血清TC、TG、LDL-C、24h尿蛋白显著高于对照组(P<0.01);辛伐他汀组血清TC、TG、LDL-C、24h尿蛋白明显低于高脂组(P<0.01),而 HDL-C则明显高于高脂组(P<0.01);高脂组大鼠肾小球系膜细胞增生,系膜区增宽,小管间质炎性细胞浸润,而辛伐他汀组病理改变较高脂组有所减轻;高脂组和辛伐他汀组大鼠肾组织中MCP-1、OPN mRNA和蛋白表达显著上调(P<0.01);而辛伐他汀组大鼠肾组织中上述指标的表达较高脂组有明显下调(P<0.05);肾组织中OPN蛋白表达与其MCP-1表达和尿蛋白量呈高度正相关。结论 辛伐他汀可能通过降低大鼠肾组织中OPN和MCP-1的表达,从而减轻小管间质巨噬细胞浸润,从而降低了高脂血症肾损害。

Abstract: Objective To investigate the expression of osteopontin (OPN) and monocyte chemoattractant protein 1(MCP-1)and the effect of simvastatin on them in diet-hypercholesterolemia rats. Methods Wistar rats were divided into three groups: control rats, cholesterol fed rats and cholesterol fed rats treated with simvastatin (10 mg ? kg-1? d -1). Twelve weeks later, we measured the 24 hours total urine protein, creatinine clearance , total serum cholesterol, LDL cholesterol.HDL cholesterol and triglycerides. kidney pathology was observed. Immunohistochemistry was used to analyse the expression of MCP -1. The expression of OPN in kidney tissue were detected by RT-PCR and western blot. Results As compared to control group rats ,the total serum cholesterol, LDL—cholesterol level, triglycerides and 24 h total urine protein increased in hypercholesterolemia group rats(P<0.01) . but it decreased significantly in simvastatin treated group compared with hypercholesterolemia group(P<0.01). the renal pathological lesion was ameliorated in simvastatin treated group; As compared to control group rats ,the expression of MCP-1 increased in cortical tubular epithelium and the expression of OPN increased in hyperlipemia group, and the expression of MCP-1 and OPN was significantly decreased in the simvastatin treated groups after 12 weeks(P<0.05). Either the expression of MCP-1 or urine protein was positively correlated with the expression of OPN in renal tissues.Conclusion The expression of OPN and MCP-1 were increased and had a close relationship with macrophage infiltration into tubulointerstitium in Hypercholesterolemia rats.Simvastatin has some protective effect partly through down regulating OPN and MCP-1 expression and reducing macrophage infiltration.