诃子对川楝子所致肝毒性的减毒作用机制初探  

Preliminary Study on Mechanism of Hepatotoxicity Attenuation of Hezi to Chuanlianzi

作　　者：乌日汉[1] 陈玉花[1] 肖田梅[1] 毕力格 丽丽[1] 孟香花 宝乐尔 韩晓静 白梅荣 Wurihan;CHEN Yuhua;XIAO Tianmei;Bilige;Lili;MENG Xianghua;Bolor;HAN Xiaojing;BAI Meirong(Inner Mongolia University for Nationalities,Key Laboratory of Ministry of Education of Mongolian Medicine R&D Engineering,Tongliao 028000,China;Key Laboratory of Ministry of Education of Mongolian Medicine R&D Engineering,Tongliao 028000,China)

机构地区：[1]内蒙古民族大学,蒙医药研发工程教育部重点实验室,内蒙古通辽028000 [2]蒙医药研发工程教育部重点实验室,内蒙古通辽028000

出　　处：《中医药信息》2022年第1期11-18,共8页Information on Traditional Chinese Medicine

基　　金：国家民委-教育部蒙医药研发重点实验室开放课题(MDK2019063);蒙药安全性评价创新团队项目(MY20190003);中央支持地方建设专项资金交叉学科建设项目(JCHXKXM001);内蒙古民族大学博士启动基金项目(BS633)。

摘　　要：目的:初步探讨诃子缓解川楝子所致肝毒性的作用机制。方法:以含有诃子和川楝子的复方三子汤中的药物为示例,将全部64只SD大鼠随机分为正常组、三子汤组、川楝子组、栀子组、诃子组、川楝子加诃子组、川楝子加栀子组和诃子加栀子组,每组8只。除正常组外,其余各给药组灌胃相应的药物溶液,连续给药21 d。观察各组药物对该组大鼠肝功能和病理形态学的影响,采用血清代谢组学的方法对大鼠血清代谢轮廓进行分析,筛选各组指标性生物标示物。结果:与正常组比较,川楝子组大鼠血清ALT、AST含量显著升高(P<0.05),其他组大鼠血清ALT、AST含量无升高趋势;肝组织HE染色结果显示,川楝子组大鼠肝组织有少量的肝细胞肿胀,三子汤和诃子组肝细胞无明显异常变化,其余各给药组可见肝细胞胞质疏松淡染;代谢组学分析结果显示,川楝子组大鼠血清样本中与肝毒性相关的溶血磷脂酰胆碱、缬氨酸和吡咯-2-羧酸明显升高;但诃子、川楝子加诃子和三子汤组中差异代谢物含量均低于川楝子组,且明显向正常水平回调。结论:诃子可降低川楝子的肝毒性,其解毒机制可能与降低血清溶血磷脂酰胆碱18∶2含量有关,可见诃子具有配伍减毒作用。Objective:To explore the mechanism of Hezi(Terminalia chebula)attenuating hepatotoxicity of Chuanlianzi(Fructus toosendan).Methods:Compound Sanzi Decoction containing the medicinal flavor of Hezi and Chuanlianzi was used for the demonstration.64 rats were randomly divided into the normal group,the Sanzi Decoction group,the Chuanlianzi group,the Zhizi(Gardenia jasminoides)group,the Hezi group,the Chuanlianzi plus Hezi group,the Chuanlianzi plus Zhizi group and the Hezi plus Zhizi group,with 8 rats in each group.After 21 days of corresponding intervention,liver function and pathomorphology were observed,and metabolic profile of the serum samples of rats were detected by the method of serum metabolomics.Indicative biomarkers were screened in each group.Results:Compared to those in the normal group,the serum contents of ALT and AST were significantly improved in the Chuanlianzi group(P<0.05);which were not increased in the other groups.HE staining showed that there was a small amount of swelling hepatocytes in the Chuanlianzi group;there were no abnormal changes in the liver cells of the Sanzi Decoction group and the Hezi group;the cytoplasm of hepatocytes was loose and light stained in the other groups.The results of metabolomics analysis showed that the serum contents of LPC,pyrrole-2-carboxylic acid and L-valine,which were associated with hepatotoxicity,were significantly increased in the Chuanlianzi group;the contents of the differential metabolites in the Hezi group,the Chuanlianzi plus Hezi group and the Sanzi Decoction group were lower than those in the Chuanlianzi group,and they were obviously reversed to normal level.Conclusion:Hezi can reduce hepatotoxicity of Chuanlianzi.The detoxification mechanism may be related to the decrease of serum LPC18∶2.Hezi has the attenuating effect.

关 键 词：诃子 川楝子 肝毒性 减毒作用 机制初探 

分 类 号：R285.5[医药卫生—中药学]