基于肝脏代谢组学探讨桦褐孔菌醇提物肝损伤机制  

Exploration of the mechanism of liver injury caused by ethanol extract of Inonotus Obliquus based on liver metabolomics

作　　者：沈子扬 赵良友 吴丹[3] 刘树民[1] 于栋华[1] SHEN Ziyang;ZHAO Liangyou;WU Dan;LIU Shumin;YU Donghua(Research Institute of Traditional Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Drug Safety Evaluation Center,Heilongjiang University of Chinese Medicine,Harbin 150040,China;The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150001,China)

机构地区：[1]黑龙江中医药大学中医药研究院,哈尔滨150040 [2]黑龙江中医药大学药物安全性评价中心,哈尔滨150040 [3]黑龙江中医药大学附属第二医院,哈尔滨150001

出　　处：《长春中医药大学学报》2024年第10期1095-1101,共7页Journal of Changchun University of Chinese Medicine

基　　金：国家自然科学基金项目(81803871);国家重点研发计划(2022YFC3502102);黑龙江省中医局青年中医药科研课题(ZHY2023-187)。

摘　　要：目的利用肝脏代谢组学技术,探寻桦褐孔菌醇提物对大鼠肝损伤的潜在作用机制。方法将SD大鼠分为对照组、桦褐孔菌醇提物高剂量组(2.0 g·kg^(-1))、中剂量组(1.0 g·kg^(-1))、低剂量组(0.5 g·kg^(-1))。每日灌胃给药1次,连续给药12周。采用超高液相色谱-飞行时间串联质谱仪对各组大鼠肝脏进行代谢组学分析,辅以生化分析和肝脏组织病理学检查。结果与对照组比较,低、中、高剂量组组织出现不同程度炎性细胞浸润,高剂量组动物肝脏出现中央静脉淤血、胆管增生和肝细胞肿胀等组织病理学变化。桦褐孔菌醇提物高剂量组及中剂量组可降低血清中白蛋白(ALB)含量,中剂量组可升高血清中谷丙转氨酶(ALT)含量,高剂量组血清中胆红素(TBIL)、谷丙转氨酶(ALT)和谷草转氨酶(AST)水平上升。通过代谢组学研究发现,肝脏样本中鉴定出30个差异性生物标志物,参与了7个代谢通路调节,其中类固醇激素生物合成、初级胆汁酸生物合成是主要代谢途径。结论桦褐孔菌醇提物可能通过类固醇激素生物合成、初级胆汁酸生物合成变化,促进炎性因子生成,引起SD大鼠出现一定程度的肝损伤,可为进一步研究桦褐孔菌醇提物肝损伤机制提供参考。Objective To explore the potential mechanism of action of the ethanol extract of Inonotus Obliquus on rat liver injury using liver metabolomics technology.Methods 40 SD rats were randomly divided into the control group,and the high-dose group(2.0 g·kg^(-1)),the medium dose group(1.0 g·kg^(-1))and the low-dose group(0.5 g·kg^(-1))of the ethanol extract of Inonotus Obliquus.The high-dose group,the medium dose group and the low-dose group of the ethanol extract of Inonotus Obliquus were administered by gavage once a day for 12 consecutive weeks.The control group was given pure water by gavage for 12 consecutive weeks.Metabolomics analysis was performed on the liver of rats in each group by ultra-high performance liquid chromatography-time of flight tandem mass spectrometer,supplemented by biochemical analysis and liver histopathological examination.Results Compared with the control group,the high-dose group,the medium dose group and the low-dose group of the ethanol extract of Inonotus Obliquus showed different degrees of inflammatory cell infiltration in the tissues.In the highdose group,the liver of animals showed histopathological changes such as central venous congestion,bile duct hyperplasia and hepatocyte swelling.The content of serum albumin(ALB)could be decreased in the high-dose group and the medium dose group,the content of serum alanine aminotransferase(ALT)could be increased in the medium dose group,and the levels of serum bilirubin(TBIL),ALT and aspartate aminotransferase(AST)could be increased in the high-dose group.Through metabolomics research,30 differential biomarkers were identified in liver samples which were involved in the regulation of 7 metabolic pathways,among which steroid hormone biosynthesis and primary bile acid biosynthesis were the main metabolic pathways.Conclusion Ethanol extract of Inonotus Obliquus may promote the production of inflammatory factors through changes of steroid hormone biosynthesis and primary bile acid biosynthesis,leading to certain degree of liver injury in SD

关 键 词：桦褐孔菌醇提物 肝脏代谢组学 肝损伤 生物标志物 初级胆汁酸 

分 类 号：R285[医药卫生—中药学]