基于尿液代谢组学分析肉豆蔻麸煨炮制前后对大鼠长期毒性的作用差异  

Differences Studied on Mechanism of Long-term Toxicity in Rats of Myristicae Semen After and Before Being Processed with Wheat Bran Based on Urinary Metabonomics

作　　者：王静[1] 陈悦 袁子民[1] 贾天柱[1] 

机构地区：[1]辽宁中医药大学,辽宁大连116600 [2]北京同仁堂科技发展有限公司,北京100079

出　　处：《中国实验方剂学杂志》2018年第4期8-13,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81274084);辽宁省自然科学基金项目(201602511)

摘　　要：目的：研究肉豆蔻麸煨炮制前后对大鼠长期毒性作用机制的差异性,探讨肉豆蔻麸煨炮制的科学内涵。方法：采用尿液代谢组学法,大鼠随机分为正常组、肉豆蔻生品组（剂量10 g·kg^-1）和麸煨品组（剂量10 g·kg^-1）,灌胃给药12周后,采集各组大鼠24 h的尿样,通过偏最小二乘法-判别分析（PLS-DA）鉴别各组代谢物谱的差异,通过变量重要性投影（VIP）发现并鉴定潜在的生物标志物。结果：由PLS-DA得分可知,生品组与正常组完全分离,麸煨品组位于二者之间,接近于正常组。鉴定了17个与肉豆蔻毒性相关的生物标志物,与正常组比较,生品组中与肾毒性相关的肌酐含量显著降低,与肝毒性相关的尿中泛酸、肉毒碱C2∶0和氨基酸代谢异常,麸煨品组对肌酐、泛酸、肉毒碱C2∶0和氨基酸代谢均有向正常组显著回调的作用。结论：肉豆蔻生品长期应用有致肝、肾毒性,而麸煨炮制可降低该毒性。Objective： To develop the differences on mechanism of long-term toxicity in rats treated with raw products and processed products with wheat bran of Myristicae Semen,and to explore the connotation about its processing technology with wheat bran.Method： A urinary metabonomics method was developed to study on longterm toxicity in rats of Myristicae Semen before and after being processing,rats were divided into three groups,including normal group,the raw products group and the processed products group with the dose of 10 g·kg^-1 for 12 weeks.Urinary samples of 24 hours after stopping the intragastric administration were collected.Partial least squares-discriminant analysis（PLS-DA） was employed to process data from all the groups,variable importance in the projection（VIP） were adopted to analyze potential biomarkers.Result： Good separation was observed between the raw products group and the normal group,the prcessed products group lied between the two groups,and was close to the normal group.Seventeen potential biomarkers related with long-term toxicity were screened out.Compared with those in the normal group,creatinine in the urine associated with renal toxicity significantly decreased in the raw products group; pantothenic acid,carnitine C2 ∶ 0 and amino acids in the urine associated with hepatotoxicity metabolized abnormally; these biomarkers in the processed products group were adjusted significantly to the normal group.Conclusion： When large amounts of the raw Myristicae Semen are taken for a long time,hepatic and renal toxicity will occur,but its toxic effects can decrease significantly after being processed with wheat bran.

关 键 词：肉豆蔻 麸煨品 肌酐 长期毒性 尿液代谢组学 炮制减毒 氨基酸 

分 类 号：R283[医药卫生—中药学] R943.1[医药卫生—中医学]