黄芪甲苷拮抗马兜铃酸Ⅰ所致的急性肾小管损伤  

Protective effect of astragaloside Ⅳ on acute tubular injury induced by aristolochic acid Ⅰ

作　　者：马莲顺[1] 肖植涛[1] 叶杰成[1] 刘梅[1] 郑广娟[2] 李楚天[2] 陆伟标[1] 陈德臻[1] 杨海峰[2] 朱林燕[1] 

机构地区：[1]暨南大学医学院药理学系,广东广州510632 [2]广东省中医院,广州中医药大学第二附属医院病理科,国家慢性肾脏病中医临床研究基地,广东广州510120

出　　处：《中国病理生理杂志》2012年第11期1966-1970,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.31070997);暨南大学科研培育与创新项目(No.21611429);广州中医药大学中医药科研创新基金资助项目(No.10CX49)

摘　　要：目的:观察黄芪甲苷对马兜铃酸Ⅰ所致的急性肾小管损伤的影响。方法:(1)体外实验:四甲基偶氮唑盐(MTT)法观察黄芪甲苷对马兜铃酸Ⅰ所致人近曲小管上皮细胞(HK-2)存活率降低的拮抗作用;(2)动物体内实验:马兜铃酸Ⅰ腹腔注射6 d建立昆明小鼠急性肾损伤模型,同时用50 mg.kg-1.d-1黄芪甲苷灌胃进行干预治疗。7 d后检测尿蛋白、尿γ-谷氨酰转移酶(γ-GT)、血清肌酐(SCr)、血尿素氮(BUN)水平的变化和肾脏组织形态学变化。结果:(1)黄芪甲苷能增加马兜铃酸Ⅰ处理的HK-2细胞存活率,并呈剂量依赖趋势;(2)黄芪甲苷干预组小鼠尿蛋白、尿γ-GT、SCr、和BUN的水平均低于马兜铃酸肾损伤组;近曲小管坏死和裸基底膜面积也较马兜铃酸肾损伤组明显改善。结论:黄芪甲苷可以拮抗马兜铃酸Ⅰ诱导的急性肾小管损伤。AIM： To study the effect of astragaloside Ⅳ（AS Ⅳ） on acute aristolochic acid nephropathy（AAN）.METHODS： MTT assay was used to observe the viability of human proximal tubule epithelial cell line HK-2 in vitro.In in vivo experiments,Kunming mice were intra peritoneally injected with aristolochic acid I（AAⅠ） for 6 d to induce acute AAN model.AS Ⅳ at dose of 50 mg·kg-1·d-1 was gavaged for 6 d,and the levels of urine protein,urine γ-glutamyltransferase（γ-GT）,serum creatinine（SCr）and blood urea nitrogen（BUN） were measured.The histological changes of the kidneys were observed under microscope by HE and periodic acid-silver methenamine（PASM） staining at the 7th day.RESULTS： The cell viability was significantly inhibited by AA I.However,the cell viability increased when AA I combined with AS Ⅳ was given as compared with control group,indicating that AS Ⅳ plays a dose-dependent protective role in HK-2 cells against the injury of AA I.The results of in vivo experiments showed that the levels of urine protein,urine γ-GT,SCr and BUN were decreased in AA I combined with AS Ⅳ group compared with AA I renal injury group.Histological study showed that AA I-induced kidney injury was improved with the decrease in the area of tubule necrosis and nude tubular basement membrane.CONCLUSION： AS Ⅳ has a protective effect on renal tubular damage induced by AA Ⅰ.

关 键 词：马兜铃酸Ⅰ 黄芪甲苷 急性肾损伤 小鼠 

分 类 号：R365[医药卫生—病理学]