肉桂多次ig给药在肾阳虚大鼠体内的积累和代谢分析  

Analysis of accumulation and metabolism of Cinnamomum cassia after multiple intragastric administration in kidney-yang deficiency rats

作　　者：张哲 汪祺[2] 陈建华 赵雯雯 孙秀蕊 韩洪翠 王雪 荆紫琪 张玉杰[1] 马双成[2] ZHANG Zhe;WANG Qi;CHEN Jianhua;ZHAO Wenwen;SUN Xiurui;HAN Hongcui;WANG Xue;JING Ziqi;ZHANG Yujie;MA Shuangcheng(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;Institute of Chinese Medicine and Ethnic Medicine,National Institutes for Food and Drug Control,Beijing 100010,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]中国食品药品检定研究院,中药民族药研究所,北京100010

出　　处：《药物评价研究》2022年第12期2450-2457,共8页Drug Evaluation Research

基　　金：国家自然科学基金面上项目(81673680)。

摘　　要：目的 考察肉桂多次ig给予肾阳虚大鼠后,鉴定大鼠肾脏、血液、尿液、粪便中原型成分和代谢产物。方法 采用ip氢化可的松方法制备大鼠肾阳虚模型,造模成功后按照生药量1.35 g·kg^(-1)·d^(-1) ig肉桂提取物,连续15 d。末次给药后,收集大鼠血浆、尿液、粪便和肾组织样品,进行UPLC-LTQ-Orbitrap-MS分析。根据色谱保留时间、精确相对分子质量、多级质谱碎片信息结合文献报道对各样本中的成分进行确认,并推测代谢物的代谢途径。结果 从肾阳虚模型大鼠各样本中共鉴定出24个成分,其中3个原型成分,21个代谢产物,包括12个原花青素类、8个木脂素类、2个二萜类、2个有机酸。结论肉桂成分在肾阳虚大鼠体内代谢广泛,代谢途径主要包括甲基化、硫酸化和葡萄糖醛酸化反应。尿液中检出的化学成分最多,其次为血液、肾组织、粪便。长期给药情况下以原型存在于靶器官和血中成分很少,推测代谢物发挥药效的可能性较大。Objective To investigate the archetypal components and metabolites in kidney,blood,urine and feces of kidney-yang deficiency rats after repeated administration with Cinnamomum cassia.Method The rat model of kidney-yang deficiency was established by intraperitoneal injection of cortisol,and the extract of C.cassia was administered at the dosage of 1.35 g·kg^(-1)·d^(-1) for15 days.Plasma,urine,fecal and renal tissue samples were collected after the last administration of the extract of C.cassia and analyzed by UPLC-LTQ-Orbitrap-MS.Based on the retention time of chromatography,accurate relative molecular mass,and multilevel mass spectrometry fragment information,the components in each sample were identified and the metabolic pathways of metabolites were inferred.Results A total of 24 components(three protypes and 21 metabolites) were identified,including 12procyanidins,8 lignans,two diterpenoids and two organic acids.Conclusion Components of C.cassia have a wide metabolism in kidney-yang deficiency rats,and the metabolic pathways mainly include methylation,sulfation and glucuronic acid reaction.Most of the chemicals were found in urine,followed by blood,kidney tissue and feces.In the case of long-term administration,there are few components in the target organs and blood in the prototype,so it is more likely that the metabolites will exert their effects.

关 键 词：肉桂 肾阳虚 代谢 积累 线性离子阱-静电场轨道阱联用质谱 

分 类 号：R285.51[医药卫生—中药学]