基于LC-MS/MS的莱菔子炮制雷公藤降低肾毒性的代谢组学研究  

Metabonomic Study of Radix Tripterygii Wilfordii Processed with RAPHANI SEMEN to Reduce Nephrotoxicity Based on LC MS/MS

作　　者：魏江平 高思佳 王计瑞 秦伟瀚[1] 郭延垒[1] 王云红[1] 花雷[1] 张小梅[1] 阳勇[1] Wei Jiangping;Gao Sijia;Wang Jirui;Qin Weihan;Guo yanlei;Wang Yunhong;Hua Lei;Zhang Xiaomei;Yang Yong(Chongqing Academy of Chinese Materia Medica,Chongqing 400065)

机构地区：[1]重庆市中药研究院,重庆400065

出　　处：《中药药理与临床》2022年第4期126-131,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重大新药创制科技专项(编号:2017ZX09101002);重庆市自然科学基金面上项目(编号:cstc2018jcyjAX0142);重庆市基本科研业务费(编号:cstc2020jxjl-jbky10003、jbky20200020)。

摘　　要：目的:探讨雷公藤被莱菔子炮制前后对正常小鼠肾毒性的影响及其潜在作用途径。方法:健康昆明种小鼠和SD种大鼠经雷公藤4 g/kg及其炮制品4 g/kg干预7 d后,收集各组小鼠血清用于肌酐和尿素氮含量检测并固定其肾组织用于病理形态学观察;采集各组大鼠血清用于血清代谢组学分析。结果:与正常对照组比较,雷公藤4 g/kg组小鼠出现肾小管上皮细胞重度肿胀或颗粒样空泡变性、管腔扩张明显且管腔内可见透明、颗粒或细胞管型,小灶性炎性细胞浸润和细胞凋亡等,其病理评分显著升高(P<0.01);血清尿素氮含量显著降低(P<0.01);血清代谢组学显示苯丙氨酸代谢、牛磺酸和低牛磺酸代谢等途径出现差异性改变;与雷公藤4 g/kg组比较,雷公藤炮制品4 g/kg组小鼠肾脏的病理变化有所改善;血清尿素氮含量明显升高(P<0.05);血清代谢组学分析表明牛磺酸和低牛磺酸代谢、泛酸和辅酶A生物合成等通路代谢显著改变(P<0.01)。结论:雷公藤炮制品降低小鼠肾毒性可能与其改变牛磺酸和低牛磺酸代谢等生物途径有关。Objective: To investigate the effect of Radix Tripterygii Wilfordii(RTW) on nephrotoxicity in normal mice and its potential pathway before and after being processed by RAPHANI SEMEN. Methods: After the healthy Kunming mice and Sprague Dawley rats were administrated with RTW(4 g/kg) and its processed product with RAPHANI SEMEN(RPSR, 4 g/kg) for one week, the serum of mice was collected for the determination of creatinine and urea nitrogen and their kidney tissues were fixed for pathomorphological observation. The serum of rats in each group was collected for metabolomic analysis. Results: Compared to the blank group, the mice in RTW 4 g/kg group showed nephrotoxicity, such as severe swelling or granulovacuolar degeneration of renal tubular epithelial cells, obvious lumen expansion, hyaline, granular or cellular cast, infiltration of small focal inflammatory cells and apoptosis, with higher pathological score(P<0.01). Additionally, the concentration of serum urea nitrogen was decreased(P<0.01). Furthermore, serum metabolomic analysis revealed differential changes in many metabolic pathways, such as phenylalanine metabolism and taurine and hypotaurine metabolism. Compared with the conditions in RTW 4 g/kg group, the pathological changes of kidney in RPSR group were improved. The concentration of serum urea nitrogen was increased(P<0.05). Moreover, serum metabolomic analysis indicated that the taurine and hypotaurine metabolism, biosynthesis of pantothenic acid and coenzyme A and other pathways were changed(P<0.01). Conclusion: The mechanism of RPSR in reducing nephrotoxicity of mice might be related to the change of biological pathways such as taurine and hypotaurine metabolism.

关 键 词：雷公藤 莱菔子 肾毒性 代谢途径 

分 类 号：R285.5[医药卫生—中药学]