醋制商陆正丁醇部位降低肝肾毒性作用机制研究  

Mechanism of n-butanol position of vinegar-processed Phytolacca acinosa on reducing hepatorenal toxicity

作　　者：丁锐 王奎龙 沈梦丹 吴鑫 吴国清[2,3,4] 曹岗[1] DING Ruil;WANG Kui-long;SHEN Meng-dan;WU Xin;WU Guo-qing;CAO Gang(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Zhejiang Academy of Traditional Chinese Medicine,Hangzhou 310007,China;Tongde Hospital of Zhejiang Province,Hangzhou 310012,China;Key Laboratory of Research and Development of New Chinese Medicine of Zhejiang Province,Hangzhou 310063,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]浙江省中医药研究院,浙江杭州310007 [3]浙江省立同德医院,浙江杭州310012 [4]浙江省中药新药研发重点实验室,浙江杭州310063

出　　处：《中草药》2023年第3期798-807,共10页Chinese Traditional and Herbal Drugs

基　　金：浙江省中医药科技计划项目(2021ZZ009),浙江省中医药科技计划项目(2021ZB086),浙江省中医药科技计划项目(2018ZY004);国家自然科学基金青年基金项目(82003947);浙江中医药大学中青年科研创新基金项目(KC201913);浙江省基础公益研究计划青山湖联合基金资助项目(LQY19H280001)。

摘　　要：目的采用代谢组学的方法探究商陆Phytolacca acinosa醋制前后正丁醇部位肝肾毒性的差异及减毒作用机制。方法采用UPLC-Q-TOF/MS的方法对商陆醋制前后正丁醇部位的成分变化进行研究。小鼠ig商陆生醋品正丁醇部位低、高剂量(27、54 mg/kg)28 d后,通过血清生化指标和病理切片评价商陆醋制前后的肝肾毒性差异;采用UPLC-Q-TOF/MS对血清进行数据采集;通过QI、HMDB及MetaboAnalyst 5.0寻找与商陆炮制减毒相关的差异代谢物及代谢通路。结果商陆醋制后部分皂苷类成分含量下降显著,并能够明显降低生品导致的肝肾功能指标的异常升高。病理切片结果显示,与对照组比较,生品组的肝、肾组织病变明显;醋制后病变程度显著减轻。通路富集分析发现胆汁酸代谢可能与商陆醋制减毒密切相关;进一步对胆汁酸进行半定量分析发现,商陆醋制后能够改善生品导致的结合型胆汁酸含量的下降及次级胆汁酸含量的升高,从而改善胆汁酸代谢紊乱。结论商陆生品具有肝肾毒性,醋制后皂苷类成分含量下降,毒性显著降低,其作用机制可能与改善胆汁酸代谢紊乱密切相关。Objective To investigate the differences of hepatorenal toxicity and mechanism of detoxification before and after vinegar of n-butanol fraction of Phytolacca acinosa based on metabolomics.Methods UPLC-Q-TOF/MS was used to study the composition changes of n-butanol fraction of P.acinosa before and after vinegar preparation.After 28 d of mice ig n-butanol fraction of raw or vinegar-processed P.acinosa(27,54 mg/kg),the difference of hepatorenal toxicity was assessed by serum biochemical indexes and pathological sections;The data of serum were collected by UPLC-Q-TOF/MS;Through QI,HMDB and MetaboAnalyst 5.0,the differential metabolites and metabolic pathways related to the processing and detoxification of P.acinosa were searched.Results The content of some saponins in vinegar-processed P.acinosa was significantly decreased,and abnormal increase of liver and kidney function indexes caused by raw product could be significantly reduced.The results of pathological section showed that pathological changes of liver and kidney tissues in raw product group were more obvious than those in control group;The degree of pathological changes was significantly reduced after vinegar-processed.The pathway enrichment analysis showed that metabolism of bile acid may be closely related to the detoxification of vinegar-processed P.acinosa;Further semi-quantitative analysis of bile acid showed that vinegar-processed P.acinosa could improve the decrease of conjugated bile acid content and increase of secondary bile acid content caused by raw products,thereby improving the metabolic disorder of bile acid.Conclusion The raw P.acinosa has hepatorenal toxicity.The content of saponins and toxicity were significantly decreased after vinegar-processed.Its mechanism may be closely related to the improvement of bile acid metabolism disorder.

关 键 词：商陆 代谢组学 肝肾毒性 醋制 商陆皂苷I 商陆皂苷R 商陆皂苷F 商陆皂苷E 商陆皂苷A 商陆皂苷M 胆汁酸 

分 类 号：R285.5[医药卫生—中药学]