柴胡疏肝散对情志应激致小鼠肝损伤的保护作用  

Protective effect of Chaihu Shugan San on emotional stress-induced liver injury

作　　者：周青青 吴燕萍 栗原博[1,2] 李怡芳 梁磊[1,2] 何蓉蓉 ZHOU Qing-qing;WU Yan-ping;HIROSHI Kurihara;LI Yi-fang;LIANG Lei;HE Rong-rong(Institute of Traditional Chinese Medicine and Natural Products,College of Pharmacy,Jinan University,Guangzhou 510632,China;Guangdong Engineering Research Center of Chinese Medicine and Disease Susceptibility,School of Traditional Chinese Medicine,Jinan University,Guangzhou 510632,China)

机构地区：[1]暨南大学药学院中药与天然药物研究所,广东广州510632 [2]暨南大学中医学院,广东省疾病易感性与中医药研发工程技术研究中心,广东广州510632

出　　处：《药学学报》2021年第11期2968-2976,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81973718,82004231);广东省自然科学基金资助项目(2021A1515011297)。

摘　　要："情志致病"是中医理论的重要组成部分,强烈的情志刺激会影响机体阴阳气血平衡,导致各种疾病的发生。柴胡疏肝散是治疗"肝气郁结"的经典名方,本研究旨在研究柴胡疏肝散对小鼠应激性肝损伤的保护作用及其可能的作用机制。实验方案经暨南大学动物实验伦理委员会批准,所有程序均严格按照动物使用和护理的伦理原则进行。实验采用急性拘束应激诱导小鼠急性肝损伤模型,使用柴胡疏肝散进行保护,检测小鼠肝损伤指标和脂质过氧化等相关指标。结果表明,柴胡疏肝散能显著改善急性拘束应激导致的小鼠肝损伤,降低血清谷丙转氨酶和谷草转氨酶水平,改善小鼠肝脏组织病理学状况和炎性浸润等情况。进一步检测脂质过氧化和生物节律因子,发现柴胡疏肝散可降低脂质过氧化产物丙二醛和4-羟基-壬烯醛的水平,同时增加谷胱甘肽的水平,改善急性拘束应激小鼠肝脏的氧化应激水平,还可以降低生物节律因子BMAL1 (brain and muscle Arnt-like protein-1)的表达,改善急性拘束应激引起的节律变化。本研究表明,柴胡疏肝散对急性拘束应激所致肝损伤的保护作用可能与其改善脂质过氧化以及调控生物节律因子等有关,为阐明柴胡疏肝散的疏肝解郁作用的科学内涵提供了实验基础,为疏肝解郁中药/复方辅助治疗肝损伤的应用和推广提供了实验依据。Chaihu Shugan San(CHSGS), a classic traditional Chinese medicinal formula, has been widely used in clinics for emotional disease. Here the protective effect and possible mechanisms of Chaihu Shugan San in stress-induced liver injury were investigated. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. Mice were administered CHSGS for 7 days and subjected to 18-h acute stress before being killed.Alanine aminotransferase(ALT), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels in serum were measured with commercial kits. Histomorphology of the liver was analyzed by hematoxylin-eosin staining and immunohistochemistry. Glutathione(GSH) content, 4-hydroxynonenal(4-HNE), brain and muscle Arnt-like protein-1(BMAL1) and arachidonate 15-lipoxygenase(ALOX15) protein were detected by LC-MS and Western blot, respectively. The results showed that CHSGS ameliorated acute stress-induced liver damage by reducing ALT and AST levels in serum and inflammatory infiltration in liver tissue. Network pharmacology analysis showed that CHSGS was associated with lipid peroxidation. Further analysis confirmed that MDA and 4-HNE levels declined and GSH level increased in livers of stressed mice after CHSGS administration. CHSGS also lowered BMAL1 expression, a pivotal factor in circadian rhythm, in livers of stressed mice. In conclusion, CHSGS ameliorated stress-induced liver injury by repressing lipid peroxidation and regulating circadian rhythm. Our studies implicate that CHSGS is promising as a therapy for stress-induced liver injury, and lay foundation for designing novel prophylactic and therapeutic strategies for stress-induced liver injury.

关 键 词：柴胡疏肝散 拘束应激 肝损伤 脂质过氧化 BMAL1 

分 类 号：R966[医药卫生—药理学]