雷洛昔芬对蛋白尿慢性肾纤维化大鼠肾脏的保护作用  

Renoprotective effects of raloxifene on rats with chronic proteinuria renal fibrosis

作　　者：唐超[1] 张伯科[1] 周琪[1] 沈雯雯[1] 梁维龙[1] 阚春明[1] 

机构地区：[1]安徽医科大学第一附属医院肾内科,合肥230022

出　　处：《安徽医科大学学报》2010年第3期363-366,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金项目(编号:070413074)

摘　　要：目的探讨雷洛昔芬对蛋白尿慢性肾纤维化大鼠肾脏的保护作用及机制。方法大鼠随机分为正常组、模型组及雷洛昔芬干预组。模型组和雷洛昔芬组给予尾静脉注射多柔比星(4mg/kg),1周后重复,制备蛋白尿慢性肾纤维化模型,雷洛昔芬组于首次注射多柔比星2周后给予雷洛昔芬[3mg/(kg.d)]灌胃。在首次多柔比星注射后第4、7、10周末测定24h尿蛋白排出量;于首次注射多柔比星后第7、10周末处死部分大鼠留取肾组织进行病理形态学和免疫组化检查。结果①雷洛昔芬组在第4、7、10周末24h尿蛋白排出量均明显低于同时点模型组(P<0.01);②10周末雷洛昔芬组肾小管-间质损伤指数(TII)明显低于同时点模型组(P<0.05);③雷洛昔芬组肾组织α平滑肌肌动蛋白明显低于同时点模型组(P<0.05),纤维连接蛋白表达具有同样的变化趋势。结论雷洛昔芬具有抑制肾纤维化的作用,可能与抑制肌成纤维细胞的生物学作用有关。Objective To study the renoprotective effects and possible mechanism of raloxifene in adriamycin-induced nephrotic rats.Methods Rats were randomly divided into control group,chronic proteinuric rats model group and proteinuric model treated with raloxifene groups.Proteinuric model was induced by a single does of adriamycin equal to 4 mg/kg and twice injected intravenously at an interval of a week afterwad,Raloxifene treatment group was given raloxifene 3 mg/kg daily intragastric administration after the second injectiong of adriamycin.Urine protein excretion was evaluated at the end of 4 th,7 th,10 th week,after the first injection of adriamycin.At the end of 7 th,10 th week,renal pathological changes were examined by HE and Masson staining,the expression of α-smooth muscle actin（α-SMA）,fibronectin（FN） were determined by immunohistochemistry.Results ① 24 h proteinuria excretion of the raloxifene treatment group was significantly lower than that in the model group at the same time （P〈0.01）.② Tubulointerstitial injury indices（TII） of the raloxifene treatment group was markedly attenuated compared with the model group at the 10th week （P〈0.05）.③ The protein levels of α-SMA in the raloxifene treatment group was significantly lower than those of the model group at the same time（P〈0.05）.The expression of FN showed similar tendency.Conclusion Raloxifene has benefical effects on reduction of renal fibrosis,and this effect may be associated with inhibition of myofibroblast biological function.

关 键 词：蛋白尿 雷洛昔芬/药理学 多柔比星 

分 类 号：R692[医药卫生—泌尿科学] R971.4[医药卫生—外科学]