环孢素A慢性肾毒性及丹参保护作用_药学论文.docVIP

环孢素A慢性肾毒性及丹参保护作用_药学论文 环孢素A慢性肾毒性及丹参保护作用_药学论文 【关键词】 环孢菌素类；药物毒性；丹参 　　摘要： 目的 探讨环孢素A(CsA)慢性肾毒性的发生机制及丹参对其的保护作用。方法 将雄性大鼠随机分为对照组、模型组及丹参组,分别给予橄榄油、CsA+葡萄糖及CsA+丹参注射液。观察给药前和给药28d后各组大鼠24h的尿量及肾功能；观察给药28d后各组大鼠血浆肾素-血管紧张素系统(RAS)及肾脏组织学变化。结果 CsA能诱导肾小球滤过率下降，增加尿中N-乙酰-β-D-氨基葡萄糖苷酶（NAG）的排泄，血浆肾素活性（PRA）、血管紧张素II（AngⅡ）水平明显升高，导致肾间质纤维化和小动脉病变等；丹参能使血浆PRA、AngⅡ水平减低，并能改善肾脏功能及病理变化；各组之间血浆醛固酮水平无变化。结论 CsA的慢性肾毒性损伤可能与RAS的激活，尤其是与AngⅡ的增加有关；丹参能使血浆PRA、AngⅡ水平降低，对CsA的慢性肾毒性有明显的保护作用。 　　关键词：环孢菌素类；药物毒性；丹参 　　Cyclosporin-induced chronic nephrotoxicity and preventive effects of salvia compound 　　Abstract： Objective To explore the mechanism of cyclosporin-induced chronic nephrotoxicity and the preventive effects of salvia compound.Methods Thirty adult male rats were randomly allocated into 3 groups.Group A received olive oil as control.The rats in group B received cyclosporin A (CsA) and glucose injection.The rats in group C received CsA and compound salvia injection.The amounts of urine in 24 hours and renal function were measured before and after the drugs were given.The levels of plasma renin activity(PRA),plasma angiotension II (Ang II) and Aldosterone(ALD) were also measured after the rats were given CsA and compound salvia injection for 28 days,and also the changes of renal tissues were assessed by histological examination.Results CsA can induce the decrease of glomerular filtration rate (GFR) ,increase the excretion of n-acetyl-β-d-glucosaminidase（NAG）in urine ,and increase the levels of PRA and Ang II in blood obviously ,and induce the tubulointerstitial fibrosis and the injury of renal arterioles .But salvia compound can decrease the levels of PRA and Ang II,improve the function of kidneys and the pathological changes .There was not significant difference in ALD levels among 3 groups.Conclusion Cyclosporin-induced chronic nephrotoxicity may be related to the activation of renin-angiotensin system (RAS) ,especially to the increase of AngⅡ levels.Salvia compound can decrease the levels of PRA and AngⅡ,and have p