龙胆泻肝汤对大鼠肾毒性的观察

The nephrotoxicity in rats caused by Longdan Xiegan decoction

目的:观察配伍不同剂量关木通的龙胆泻肝汤给药不同时间的大鼠肾功能和组织形态学变化。方法:用配伍不同剂量关木通的龙胆泻肝汤水煎剂按原药材每天13,14.5,17.5 g.kg-1剂量(其中含关木通分别为1.5,3,6 g.kg-1)给大鼠灌胃,连续12周,分别于给药第4,8,12周测定大鼠肾功能指标,观察肾脏组织形态学改变。结果:龙胆泻肝汤中配伍小剂量关木通(1.5 g.kg-1)连续用药12周,未见肾功能明显损伤;配伍中剂量关木通(3 g.kg-1)连续用药12周,肾近曲小管上皮细胞出现轻微损害;大剂量的关木通(6 g.kg-1)连续用药4周即出现明显的肾损伤,且随着给药时间的延长,损伤程度逐渐加重;病理观察到肾损伤的部位主要是皮髓交界处的近曲肾小管。结论:龙胆泻肝汤的肾毒性与其关木通配伍用量和服药时间相关。龙胆泻肝汤中配伍小量关木通在较短时间内具有相对安全性,而大剂量使用关木通可引起肾损害。

Objective： To observe the renal injury in rats induced by Longdan Xiegan decoction （LDXGD） containing different dosages Adstolochia manshriensis. Method： SD rats were divided into four groups at random, and were fed with three kinds of LDXGD 13, 14.5, 17.5 g·kg^-1（containing respectively A. manshriensis 1.5, 3, 6g·kg^-1） and distilled water respectively for 12 weeks. Renal functional parameters on 4,8, 12 w were determined and changes of histomorphology in rats on the end of experiment were observed. Result： The LDXGD containing low dose （1.5 g·kg^-1） A. manshriensis did＇t induce significantly renal injury in rats during 12 weeks; the LDXGD containing midst dose（3 g·kg^-1 ） A. manshriensis induced light damage of proximal convoluted tubule epithelial cells in rats during 12 weeks; the LDXGD containing high dose（6 g·kg^-1） A. manshriensis induced significantly renal injury in rats after administed 4 weeks. Along with the lasting of administration, the degree of injury became more seriously. The main renal injury location was in proximal convoluted tubule. Conclusion： The renal toxicity of LDXGD is correlated with the dose of A. manshriensis and the time of administration. The LDXGD containing low dose A. manshriensis has relative security. However, the LDXGD containing high dose A. manshriensis can induce renal injury.