地灵丹汤对单侧输尿管梗阻大鼠模型肾间质纤维化的防治作用  

Dilingdan Decoction prevents renal interstitial fibrosis in a rat model of unilateral ureteral obstruction

作　　者：宦红娣[1] 张景红[1] 郑士荣[1] 孟巍巍[1] 张军力[1] 

机构地区：[1]中国人民解放军第八五医院肾内科,上海200052

出　　处：《中西医结合学报》2008年第5期493-497,共5页Journal of Chinese Integrative Medicine

基　　金：上海市医学发展基金资助项目(No2003ZD002)

摘　　要：目的:研究中药复方地灵丹汤对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)致肾间质纤维化模型大鼠肾间质纤维化的防治作用及其可能机制。方法:将60只SD大鼠随机分为假手术组、模型组、依那普利组及地灵丹组。采用UUO法建立肾间质纤维化大鼠模型,观察血尿素氮、血清肌酐和24h尿蛋白定量及肾组织病理改变,并采用免疫组织化学法检测转化生长因子β1(transforming growth factor-β1,TGF-β1)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、纤维连接蛋白(fibronectin,FN)及层黏连蛋白(laminin,LN)的表达。结果:第7天模型组肾间质大量炎症细胞浸润及胶原表达,TGF-β1、FN和LN表达面积百分率较假手术组明显增加(P<0.05);地灵丹组间质纤维化面积较模型组减少(P<0.05)。第14天地灵丹组和依那普利组肾间质TGF-β1、α-SMA、FN和LN表达面积百分率较模型组减少(P<0.05),BUN、SCr和24h尿蛋白无明显差异。第21天地灵丹组SCr、肾间质纤维化和TGF-β1表达面积百分率较依那普利组和模型组下降(P<0.05)。结论:地灵丹能减轻单侧输尿管梗阻模型大鼠的蛋白尿和肾间质纤维化,抑制TGF-β1、α-SMA、FN和LN的表达。在较长时间应用后,地灵丹对模型大鼠的肾功能保护作用优于依那普利。Objective： To investigate the preventive and therapeutic effects and the possible mechanisms of Dilingdan Decoction （DLDD）, a compound Chinese herbal medicine, on rats with renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction （UUO）. Methods： Sixty SD rats were randomly divided into sham-operated group, untreated group, enalapril-treated group and DLDD-treated group. Blood urea nitrogen （BUN）, serum creatinine （SCr）, urine protein quantization in 24 hours and pathological changes of the obstructed kidney were observed. The expressions of transforming growth factor-β1 （TGF-β1）, alpha-smooth muscle actin （α-SMA）, fibronectin （FN） and laminin （LN） were detected by immunohistochemical method and colored-multimedia pathological image analysis system. Results： Massive inflammatory infiltrates and collagen expression in renal interstitial in the untreated group were observed on the 7th day. Compared with the sham-operated group, percentages of area of TGF-β1,α- SMA, FN and LN expressions in the untreated group were markedly increased （P〈0. 05）, while the percentage of area of interstitial fibrosis was decreased in the DLDD-treated group as compared with the untreated group （P〈0.05）. On the 14th day, the percentages of area of TGF-β1, α-SMA, FN and LN expressions were declined in two treated groups as compared with the untreated group （P〈0. 05）, but had no statistical difference in biochemical indicators, including BUN, SCr and 24-hour urinary protein. On the 21st day, the level of SCr and the percentage of area of TGF-β1 expression in the DLDD-treated group were lower than those of the enalapril-treated group （P〈0. 05）. Conclusion： DLDD can reduce the excretion of urinary protein and the degree of interstitial fibrosis, and significantly inhibit the expressions of TGF-β1,α-SMA, FN and LN. DLDD is superior to enalapril in protecting renal function after long-time application in rats.

关 键 词：地灵丹 肾间质纤维化 转化生长因子β1 Α-平滑肌肌动蛋白 纤维连接蛋白 层黏连蛋白 大鼠 

分 类 号：R285[医药卫生—中药学]