川芎嗪、泼尼松和贝那普利对马兜铃酸致大鼠急性肾小管坏死的干预作用比较  

Comparative effects among ligustrazine, prednisone and benazepril on acute renal tubular necrosis induced by aristolocbic acid in rats

作　　者：万晨旭[1] 张金元[2] 

机构地区：[1]南京军区南京总医院解放军肾脏病研究所,210002 [2]上海解放军第四五五医院南京军区肾脏病专科中心

出　　处：《中华肾脏病杂志》2006年第7期426-429,共4页Chinese Journal of Nephrology

基　　金：中国博士后科学基金资助项目(2004035666);上海市科学技术发展基金资助项目(20034060)

摘　　要：目的建立关木通所含马兜铃酸(AA)致大鼠急性肾小管坏死(ATN)实验动物模型,并观察和比较川芎嗪、泼尼松和贝那普利对大鼠肾小管的保护作用。方法将雄性SD大鼠随机分为6组,每组12只。正常组予蒸馏水3 ml／d灌胃;模型组、泼尼松组、贝那普利组、川芎嗪Ⅰ组和川芎嗪Ⅱ组均先予关木通水煎剂(含生药2 g／ml、AA 0．54 mg／ml、AA-I 0．46 mg／ml) 5 g·kg-1·d-1灌胃60 d,再予10 g·kg-1·d-1灌胃30 d。灌关木通2 h后,正常组与模型组予生理盐水灌胃,其余4组分别予泼尼松5 mg·kg-1·d-1、贝那普利1．7 mg·kg-1·d-1、川芎嗪50 mg·kg-1·d-1和川芎嗪150 mg·kg-1·d-1灌胃。于90 d后进行肾组织病理检查。结果正常组为正常肾组织。模型组光镜可见近曲肾小管上皮细胞成片状空泡变性,刷状缘紊乱、消失,管腔内可见脱落的上皮细胞,肾小管基膜(TBM)裸露、部分断裂、个别增厚及萎缩;肾间质轻度水肿、多灶性炎细胞浸润;肾小球系膜细胞局灶节段性轻、中度增生和系膜基质轻度增多;部分小叶间动脉管壁增厚。其余4组与模型组比较,病变均明显减轻,表现为近曲肾小管上皮细胞空泡变性明显减少,少部分刷状缘紊乱、消失,个别管腔内可见脱落的上皮细胞,个别TBM断裂及增厚减轻;肾间质炎细胞减少或消失。模型组电镜可见近曲小管上皮细胞空泡变性和脂肪变性,线粒体肿胀,细胞器减少,细胞核碎裂,细胞凋亡;间质中可见炎细胞浸润(吞噬细胞与淋巴细胞)和淋巴细胞浸入到上皮细胞中;小叶间动脉管壁增厚、管腔狭窄。其余4组与模型组比较,近曲小管上皮细胞轻度空泡变性、个别线粒体肿胀,个别细胞核轻度固缩、大部分正常;间质中可见少量吞噬细胞和淋巴细胞。其中以川芎嗪Ⅱ组和泼尼松组病变减轻尤为显著。结论(1)模型组光镜和电镜结果主要表现为ATN,表明成功建立了大鼠ATN实验动物模型Objective To establish the experimental animal model of acute tubular necrosis （ATN） in rats induced by caulis aristolochiae manshuriensis （CAM） containting aristolochic acid （AA） and compare the interventional effects among ligustrazine, prednisone and benazepril. Methods Male SD rats were divided randomly into six groups, 12 rats in each group. Control group, model group, prednisone group, benazepril group, ligustrazine Ⅰgroup and ligustrazine Ⅱ group were given respectively by gavage with 3 ml/d distilled water,5g·kg^-1·d^-1 CAM decoction （CAM 2 g/ml, AA 054 mg/ml, AA-Ⅰ 0.46 mg/ml） for 60 days, then 3 ml/d distilled water, 10g·kg^-1·d^-1 CAM decoction for 30 days. Two hours after CAM gavage, control group and model group were given with normal saline. Prednisone group, benazepril group, ligustrazine group and ligustrazine Ⅱ group were given with prednisone 5mg·kg^-1·d^-1, benazepfil 1.7mg·kg^-1·d^-1, ligustrazine 50mg·kg^-1·d^-1, ligustmzine 150 mg·kg^-1·d^-1respectively by gavage for 90 days.Histopathology of kidney tissue was examined after 90 days. Results The renal tissue of control group was normal. Light microscopy of model group revealed patchy vacuolar changes of cells from proximal convoluted tubular epithelium, disorder and loss of brush border, exfoliated epithelial cells in the lumina, exposure of areas of denuded and rupture and thickness and atrophy of tubular basement membrane （TBM）, edema and infiltration of inflammatory cells in the interstitium, focal segmental proliferation of glomemlar mesangial cells and increase of mesangial matrix, part thickness of interlobular arterial walls. The above abnormalities of other four groups were significantly attenuated compared to model group. Electron microscopy of model group revealed patchy vacuolar changes and fatty degeneration of cells from proximal convoluted tubular epithelium,sweUing of mitonchondria, reduce of organelle, karyorrhexis, apoptosis, infiltration of inflammatory cells （phagocytes and lymphocy

关 键 词：关木通 马兜铃酸 肾小管坏死 急性 川芎嗪 泼尼松 贝那普利 

分 类 号：R692.6[医药卫生—泌尿科学]