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作者中文名	作者英文名	单位中文名	单位英文名	E-Mail
侯红平	HOU Hong-ping	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
王彩霞	WANG Cai-xia	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
魏晓露	WEI Xiao-lu	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
高云航	GAO Yun-hang	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
赵晓晓	ZHAO Xiao-xiao	河北御芝林生物科技有限公司，河北石家庄 050035	Hebei Yuzhilin Biotech Co., Ltd., Shijiazhuang 050035, China
宋玲	SONG Ling	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
陈腾飞	CHEN Teng-fei	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
练东银	LIAN Dong-yin	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
李丽丽	LI Li-li	河北御芝林生物科技有限公司，河北石家庄 050035	Hebei Yuzhilin Biotech Co., Ltd., Shijiazhuang 050035, China
彭博*	PENG Bo	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
张广平	ZHANG Guang-ping	中国中医科科学院中药研究所，北京 100700	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

基金项目:中央级公益性科研院所基本科研业务费专项基金项目（ZZ13-YQ-060，ZXKT21020）

中文摘要:目的通过高分辨非靶代谢组学方法探讨臻通集胶囊对高脂血症模型大鼠的作用特点和机制。方法无特定病原体级SD大鼠40只，随机取6只作为对照组，给予正常饲料，其余所有大鼠给予高脂饲料喂养，连续4周造模成功后，分为模型组和给药组。高、中、低剂量给药组大鼠分别灌胃给予臻通集胶囊0.432、0.216、0.108 g·kg^–1，每日1次，连续给药8周。末次给药后将动物麻醉，腹主动脉采血，离心分离血清，全自动生化仪检测血清中血脂水平。取部分肝组织用于高分辨非靶代谢组学的研究。结果臻通集胶囊给药后，高、中剂量组大鼠的三酰甘油、胆固醇、低密度脂蛋白，高剂量大鼠的高密度脂蛋白较模型组明显降低，且差异具有统计学意义。与对照组比较，模型组大鼠共检测出138个差异代谢物；与模型组比较，给药组大鼠共检测出123个差异代谢物，正离子模式的72个差异代谢物有24个在给药后得到了纠正，负离子模式的51个差异代谢物有9个在给药后得到了纠正。代谢过程涉及多个信号通路，主要包括哺乳动物雷帕霉素靶蛋白（mTOR）、环磷酸鸟苷酸依赖性蛋白激酶（cGMP-PKG）、叉头框蛋白O（FoxO）、蛋白质消化和吸收、嘧啶代谢、微生物消化和吸收、甘油磷脂代谢、氨基酸生物合成、嘌呤代谢等信号通路。结论臻通集胶囊能够有效改善高脂血症大鼠的血脂水平，与其能够调节嘌呤代谢、嘧啶代谢、甘油磷脂代谢、mTOR信号通路，cGMP-PKG信号通路等密切相关。

中文关键词:高脂血症臻通集胶囊血脂水平代谢组学

Effect of Zhentongji Capsules on Hyperlipidemia Model Rats by High-resolution Untargeted Metabolomics

Abstract:Objective To explore the characteristics and mechanism of Zhentongji Capsules on hyperlipidemia model rats by high-resolution untargeted metabolomics.Methods Forty SPF SD rats were used in this experiment. Six animals were randomly assigned to the control group and fed on a normal diet, and the remaining rats were given high-fat food. After modeling for four weeks, the model rats were divided into a model group and high-, medium-, and low-dose Zhentongji Capsules groups (0.432, 0.216, 0.108 g·kg^–1). Drug intervention was carried out by gavage, once a day for eight weeks. After the last administration, the animals were anesthetized, and blood samples were collected from the abdominal aorta. The serum was centrifuged, and the blood lipid level in the serum was detected by the automatic biochemical analyzer. Some liver tissues were taken for the study of high-resolution untargeted metabolomics.Results After the administration of Zhentongji Capsules, the levels of triglyceride, cholesterol, and low-density lipoprotein in the high- and medium-dose Zhentongji Capsules groups and high-density lipoprotein in the high-dose Zhentongji Capsules group were significantly lower than those in the model group. Compared with the results in the control group, 138 differential metabolites were detected in the model group. Compared with the results in the model group, 123 differential metabolites were detected in the treatment groups. Twenty-four of 72 differential metabolites in the positive ion mode and nine of 51 differential metabolites in the negative ion mode were corrected after administration. The metabolic processes involved multiple signaling pathways, mainly including mammalian target of rapamycin (mTOR) signaling pathway, cyclic 3',5'- guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway, forkhead transcription factor O (FoxO) signaling pathway, protein digestion and absorption, pyrimidine metabolism, microbial digestion and absorption, glycerol phospholipid metabolism, amino acid biosynthesis, and purine metabolism.Conclusion Zhentongji Capsules can effectively improve the blood lipid level of hyperlipidemia rats, which was closely related to its ability to regulate purine metabolism, pyrimidine metabolism, glycerol phosphatide metabolism, mTOR signaling pathway, and cGMP-PKG signaling pathway.

keywords:hyperlipidemia Zhentongji Capsules blood lipid level metabolomics

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