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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 chronic renal toxicity of acute RAPD and different doses of RAFE. METHODS: Conventional acute toxicity assays and different doses of RAFE (25.0, 12.0, 2.00 mg·kg-1·d-1) and total aristolochic acid (10.0 mg) were used. ·kg-1·d-1) Rats were given intermittent intragastric administration for 13 weeks. Blood, urine, and kidney tissue specimens were collected at 4, 8 and 13 weeks after administration, and relevant renal functions and histological changes were examined. Results: The LD50 of RAFE was 36.8 g·kg-1, and the 95% confidence limit of LD50 was 38.8 to 2.8 g.kg-1; the renal function was changed to nitrogen in different doses of RAFE. Hyperlipidemia, massive proteinuria, and increased urinary NAG enzymes. Renal histomorphology: In the early, middle, high dose, and total acid groups, acute renal tubular necrosis, mainly in the junction of cortex and medulla, predominantly occurred, and some renal interstitial fibrosis was observed. Conclusion: NAG can be used as one of the observation indexes of early renal injury in rats; intermittent and intragastric administration of large doses of RAFE for 13 weeks can cause renal tubular dysfunction.