【摘要】 目的观察高脂血症肾损害大鼠应用舒降之治疗后一氧化氮(NO)和内皮素(ET)的变化,以探讨舒降之防治高脂血症肾损害的机制。方法将30只雄性Wistar大鼠随机分为正常对照组、高脂模型组和舒降之治疗组[2.5mg/(kg.d)],每组10只,观察12周。实验中监测各组大鼠血脂、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)及24 h尿蛋白排出量(UPE)等变化,并进行肾组织光镜检查,同时观察血、尿和肾组织匀浆中NO和ET的改变。结果舒降之治疗组的血脂水平较高脂模型组明显降低(P<0.01);UPE、尿NAG明显减少(均P<0.01);肾指数下降(P<0.05);血、尿及肾组织NO明显升高,而尿及肾组织匀浆中ET含量明显降低(均P<0.05)。光镜检查示高脂模型组大鼠肾小球系膜区增宽、系膜细胞增生、肾小管扩张、血管周围及间质细胞浸润,而舒降之治疗组上述病变明显好转。结论舒降之能明显减轻高脂血症肾损害,它能提高血清、尿及肾组织的NO水平并降低ET的水平,NO和ET的变化可能是其防治高脂血症肾损害的重要机制之一。更多还原

【Abstract】 Objective To evaluate the changes of nitric oxide (NO) and endothelin(ET) after treatment with zocor simvastatin in kidney damaged rats fed with hypercholesterol diet and study the mechanism of zocor simvastatin preventing and treating hyperlipidemia-induced renal injury.Methods 30 male Wistar rats were randomly divided into control group(n=10,normal diet),hyperlipidemia group(n=10,high-cholesterol diet) and treatment group(n=10,high-cholesterol diet plus zocor simvastatin 2.5 mg/[kg·d]).During 12 weeks of the experiment,serum lipids,urinary NAG,24-h urinary protein excretion(UPE) and histological changes under light microscopy were compared among the 3 groups.Simultaneously,the levels of NO and ET in serum,urine and renal homogenate were also measured.Results After 12 weeks of treatment with simvastatin,the level of serum lipids,and urinary NAG,UPE and renal index were all decreased as compared with those in hyperlipidemia group(all P<0.01).Light microscopy revealed no distinct width of glomerulus mesangium region,no proliferation of mesangial cells,no dilatation of renal tubules and perivascular and interstitial cell infiltration.In addition,the NO levels in serum,urine and renal homogenate were increased significantly,while the ET level in urine and renal homogenate was markedly decreased as compared with those in hyperlipidemia group(P<0.05).Conclusion Simvastatin could effectively ameliorate the hyperlipidemia-induced renal injury,increase NO and decrease ET.The changes of NO and ET may play a role in the pathogenesis and progress of hyperlipidemia-induced renal injury.更多还原