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柴胡疏肝散调节磷脂和胆汁酸代谢以对抗大鼠慢性不可预测应激诱导的肝损伤。

Chaihu-Shu-Gan-San regulates phospholipids and bile acid metabolism against hepatic injury induced by chronic unpredictable stress in rat.

作者信息

Jia Hong-Mei, Yu Meng, Ma Li-Yan, Zhang Hong-Wu, Zou Zhong-Mei

机构信息

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Oct 1;1064:14-21. doi: 10.1016/j.jchromb.2017.08.003. Epub 2017 Aug 31.

DOI:10.1016/j.jchromb.2017.08.003
PMID:28886478
Abstract

Chaihu-Shu-Gan-San (CSGS) is a famous classic traditional Chinese medicines (TCM) formula for treatment of liver stagnancy recorded in a famous book of traditional Chinese medicine, Jing Yue Quan Shu published in 1624. It has been extensively accepted as an antidepressant in China and its mechanism of action is still not clear. Previously we have found that hepatic injury happens in chronic unpredicted mild stress (CUMS). Thus, the protection of CSGS against hepatic injury induced by CUMS treatment was explored by metabonomics study and gene expression of the rat liver tissue. The results indicated that CSGS improved 8 of the 18 perturbed potential biomarkers in liver tissues of rats treated with CUMS, and involved in regulating phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. The expressions of two apoptosis associated genes (Bcl-2 and Bax) and four genes (Pnpla6, Pla2g15, Baat and Gad1) related to the perturbed metabolic pathways were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Both metabonomics and studies of genetic influences on metabolites demonstrated that CSGS inhibited hepatocyte apoptosis, and regulated phospholipids and bile acid metabolism against hepatic injury induced by CUMS in rat. Exploring the protection of CSGS against hepatic injury related to depression further clarify the relationship between CUMS-induced depression and hepatic injury, and also provide a novel insight to understand the underlying antidepressive mechanism of CSGS.

摘要

柴胡疏肝散(CSGS)是1624年出版的著名中医典籍《景岳全书》中记载的治疗肝郁的经典传统中药方剂。在中国,它已被广泛认可为一种抗抑郁药,但其作用机制仍不清楚。此前我们发现,慢性不可预测轻度应激(CUMS)会导致肝损伤。因此,通过代谢组学研究和大鼠肝组织基因表达,探讨了柴胡疏肝散对CUMS诱导的肝损伤的保护作用。结果表明,柴胡疏肝散改善了CUMS处理大鼠肝组织中18种受干扰潜在生物标志物中的8种,并参与调节磷脂和胆汁酸代谢,以对抗大鼠CUMS诱导的肝损伤。通过定量实时聚合酶链反应(qRT-PCR)进一步研究了与受干扰代谢途径相关的两个凋亡相关基因(Bcl-2和Bax)和四个基因(Pnpla6、Pla2g15、Baat和Gad1)的表达。代谢组学和基因对代谢物影响的研究均表明,柴胡疏肝散抑制肝细胞凋亡,并调节磷脂和胆汁酸代谢,以对抗大鼠CUMS诱导的肝损伤。探索柴胡疏肝散对与抑郁症相关的肝损伤的保护作用,进一步阐明了CUMS诱导的抑郁症与肝损伤之间的关系,也为理解柴胡疏肝散潜在的抗抑郁机制提供了新的见解。

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