广防己致大鼠慢性肾小管-间质损伤的实验研究Ⅰ  

Experimental study of chronic renal tubular-interstitial injuryinduced by Radix Aristolochiae Fangchi extract in rats

作　　者：杜贵友[1] 周素娟[1] 赵雍[1] 崔海峰[1] 王秀荣[1] 李丽[1] 肖永庆[1] 曹春雨[1] 张春颖[1] 吴子伦[1] 高双荣[1] 贺蓉[1] 回连强[1] 刘保延[2] 

机构地区：[1]中国中医研究院中药研究所,北京100700 [2]中国中医研究院,北京100700

出　　处：《中国中药杂志》2005年第8期610-613,共4页China Journal of Chinese Materia Medica

基　　金：国家中医药管理局中医药科技重大专项 (国中医药科 2 0 0 1ZDZX)

摘　　要：目的:　观察广防己醇提取物(RAFE)急性以及不同剂量的RAFE对肾脏慢性毒性。方法:采用常规的急性毒性实验方法和用不同剂量的RAFE(2 5 . 0 ,12 .0 0 ,2 0 0. 0mg·kg-1·d-1)以及马兜铃总酸(10. 0mg·kg-1·d-1)给大鼠间断灌胃13周,分别于给药第4 ,8,13周留取血、尿和肾组织标本,检测相关肾功能和组织学变化。结果:RAFE的LD50 为36. 8g·kg-1,LD50 95 %可信限为38 .8～2 .8 .9g·kg-1;不同剂量的RAFE作用早期,大鼠肾功能改变为氮质血症、大量蛋白尿以及尿NAG酶升高。肾脏组织形态学:中、大剂量和总酸组给药早期主要表现以皮髓质交界为主的急性肾小管坏死,而后可见部分动物肾间质纤维化。结论:NAG可作为大鼠早期肾功能损伤的观测指标之一;RAFE中、大剂量间断灌胃13周均可导致大鼠肾小管功能损害。Objective: To observe the acute and chronic renal toxicity induced by Radix Aristolochiae Fangchi Extract(RAFE) in different doses in rats.Method: The conventional method of acute toxicity was used. RAFE at the dose of 25.0 mg·kg^(-1)·d^(-1), 120.0 mg·kg^(-1)·d^(-1) and 200.0 mg·kg^(-1)·d^(-1) and aristolochic acid (AA, 10.0 mg·kg^(-1)·d^(-1)) were interruptedly administrated to rats for 13 week by gastric tube, and the sample of blood, urine and kidney were collected at 4week, 8week and 13week respectively. The indexes of renal function were measured and the morphology of kidney was observed.Result: LD (50) of RAFE was 36.8 g·kg^(-1)(the crude drug) and the 95% confidence limit was 38.8～28.9 g·kg^(-1). The changes of renal functions were azotemia, massive proteinuria and the increase of urinary NAGase(beta-N-acetylglucosaminidase) in the earlier period of administration with RAFE in rats. Pathological changes of renal tissue were as follows: acute renal tubular necrosis mainly in the boundary of cortex and medulla was observed in the earlier period, and with the elongation of administration, the pathological process of renal interstitial fibrosis observed in the middle and high groups of RAFE and AA group. Conclusion: RAFE at middle and high doses administrated by interrupted gavage above 13week can cause the injury of renal tubular functions in rats.NAGase can be used as one of observation targets in the earlier period of renal injury.

关 键 词：肾小管-间质损伤 广防己 大鼠 实验研究 急性肾小管坏死 早期肾功能损伤 肾小管功能损害 不同剂量 95%可信限 肾间质纤维化 组织学变化 肾功能改变 尿NAG酶 大量蛋白尿 组织形态学 慢性毒性 醇提取物 实验方法 急性毒性 

分 类 号：R285.5[医药卫生—中药学]