The present study aims to investigate the protective effects of Dendrobine and its underlying mechanisms on liver injury induced by isoniazid (INH) and rifampicin (RIF). A mouse model of liver injury was induced by intragastrically administration of 100 mg/kg INH and 100 mg/kg RIF for 14 days. The mice were intragastrically administrated with Dendrobine (50, 100, and 200 mg/kg) before the administration of INH and RIF. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Oxidative stress markers including glutathione, superoxide dismutase, and malondialdehyde in the liver were measured and liver histopathological examinations were performed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were applied to determine the mRNA and protein expressions, respectively. Luciferase reporter assay was used to evaluate the interactions between miR-295-5p and CYP1A2. Dendrobine significantly decreased serum ALT and AST and inhibited the liver index and ameliorated the liver histological changes induced by INH and RIF. Besides, Dendrobine also regulated oxidative stress status in the liver by the regulation of CYP1A2. Moreover, mmu-miR-295-5p was identified to target CYP1A2 and to regulate the expression of CYP1A2. In summary, Dendrobine ameliorated INH and RIF induced mouse liver injury by miR-295-5p-mediated CYP1A2 expression.

本研究旨在探讨Dendrobine对异烟肼（INH）和利福平（RIF）所致肝损伤的保护作用及其潜在机制。通过胃内施用100 mg / kg INH和100 mg / kg RIF诱导小鼠肝损伤模型，持续14天。在给予INH和RIF之前，给小鼠灌胃给予Dendrobine（50、100和200 mg / kg）。测定血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。测量肝脏中的氧化应激标志物，包括谷胱甘肽，超氧化物歧化酶和丙二醛，并进行肝脏组织病理学检查。定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹分别用于确定mRNA和蛋白质表达。萤光素酶报告基因分析用于评估miR-295-5p与CYP1A2之间的相互作用。Dendrobine显着降低血清ALT和AST，抑制肝脏指数，并改善INH和RIF诱导的肝脏组织学变化。此外，Dendrobine还通过调节CYP1A2来调节肝脏的氧化应激状态。此外，mmu-miR-295-5p被鉴定为靶向CYP1A2并调节CYP1A2的表达。总之，Dendrobine通过miR-295-5p介导的CYP1A2表达改善了INH和RIF诱导的小鼠肝损伤。Dendrobine还通过调节CYP1A2来调节肝脏中的氧化应激状态。此外，mmu-miR-295-5p被鉴定为靶向CYP1A2并调节CYP1A2的表达。总之，Dendrobine通过miR-295-5p介导的CYP1A2表达改善了INH和RIF诱导的小鼠肝损伤。Dendrobine还通过调节CYP1A2来调节肝脏中的氧化应激状态。此外，mmu-miR-295-5p被鉴定为靶向CYP1A2并调节CYP1A2的表达。总之，Dendrobine通过miR-295-5p介导的CYP1A2表达改善了INH和RIF诱导的小鼠肝损伤。