辛伐他汀降低脂质肾损害大鼠肾组织中骨调素表达  

Simvastatin decreases osteopontin expression in lipid-induced rats renal injury

作　　者：陈利群[1] 甘华[1] 吕智美[1] 

机构地区：[1]重庆医科大学附属第一医院肾内科,重庆400016

出　　处：《基础医学与临床》2010年第12期1293-1298,共6页Basic and Clinical Medicine

基　　金：重庆市卫生局项目(05-2-136)

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OPNmRNA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、24 h尿蛋白显著高于对照组(P<0.01);辛伐他汀组血清TC、TG、LDL-C、24 h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、OPNmRNA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。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· d）].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（P0.01）.but it decreased significantly in simvastatin treated group as compared with hypercholesterolemia group（P0.01）.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 hyperlipemiagroup,and the expression of MCP-1 and OPN was significantly decreased in the simvastatin treated groups after 12 weeks（P0.05）.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 was increased and had a close relationship with macrophage infiltration into tubulointerstitium in Hypercholesterolemia rats.Simvastatin has some protective effects through down regulating OPN and MCP-1 expression and reducing macrophage infiltration.

关 键 词：高脂血症 辛伐他汀 骨调素 

分 类 号：R96[医药卫生—药理学]