雷洛昔芬对多柔比星诱导大鼠蛋白尿肾损害的作用及部分机制研究  

Renoprotective effects of raloxifene on the progression of kidney disease injured by adriamycin-induced proteinuria in rats

作　　者：王芳[1] 张伯科[1] 王显[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,安徽合肥230022

出　　处：《安徽医药》2010年第11期1260-1262,共3页Anhui Medical and Pharmaceutical Journal

基　　金：安徽省自然科学基金(No070413074)

摘　　要：目的观察雷洛昔芬(raloxifene,RAL)在大鼠多柔比星(adriamycin,ARD)诱导的蛋白尿肾损害过程中是否具有肾保护作用,并进一步探讨部分可能的机制。方法大鼠随机分为:正常对照组(A组,5只)、模型组(B组,8只)、RAL治疗组(C组,8只)。实验起始第1、2周的第一天,重复给予B,C组大鼠ARD(4 mg.kg-1)尾静脉注射。自首次注射ARD之日起第二周末C组给予RAL3.0 mg.kg-1.d-1灌胃。首次给予ARD后7周末收集24 h尿标本后取肾组织标本。BCA法检测24 h尿蛋白,Masson染色并在光镜下观察肾组织病理形态学改变,并采用肾小球硬化指数(glomerulosclerotic index,GSI)及肾小管间质损伤指数(tubulointerstitial injure index,TII)评估肾脏损害程度;免疫组化检测肾组织中Ⅰ型胶原蛋白表达。结果与A组相比,第七周末B组光镜下观察肾组织形态可见系膜区细胞及基质明显增多,肾小管多灶性萎缩和片状扩张,管腔内可见蛋白管型,间质出现大量炎性细胞浸润。GSI及TII值、24 h蛋白尿排出率及Ⅰ型胶原蛋白表达水平明显升高(P<0.01);C组中上述变化均较B组有所减轻(P<0.05)。结论 RAL在大鼠多柔比星诱导的蛋白尿肾损害过程中表现出降低尿蛋白排泄率及改善肾纤维化病变的肾保护作用。Aim To investigate the potential renoprotective effects of raloxifene on the progression of kidney disease injured by adriamycin-induced proteinuria in rats,and to explore the possible mechanism.Methods Rats were assigned to three groups randomly：normal control group（group A,n=5）,model group（group B,n=8） and RAL treatment group（group C,n=8）.Rats in group B and C were given ARD 4 mg·kg^-1 via tail vein at the first day of the 1st and 2nd week,respectively.Group C received RAL treatment 3.0 mg·kg^-1·d^-1 orally in the 2nd week after the first adriamycin injection.The changes of 24 h urine protein,renal pathology and expression of type I collagen were evaluated in the end of 7th week after the first administration of adriamycin.Results In comparison with group A,in group B,the proliferation of the mesangial cells,the accumulation of the extracellular matrix,the atrophy or extension of renal tubules and infiltration of inflammatory cells in interstitium were obviously observed.The level of GSI,TII,24h urine protein excretion rate and the expression of Collagen I were significantly increased（P〈0.01）.These changes above were ameliorated by treatment with RAL（P〈0.05） in the end of 7th week after the first administration of adriamycin.Conclusion Raloxifene shows positive effects on the progressive renal disease injured by adriamycin-induced proteinuria.The mechanism may be associated with inhibiting urine protein excretion and ameliorating the changes of pathomorphology.

关 键 词：雷洛昔芬 多柔比星 蛋白尿 

分 类 号：R965[医药卫生—药理学]