通体沉香醇提物对氟尿嘧啶致小鼠肝损伤的保护作用  

Protective effect of whole-tree agarwood-inducing technique-produced agarwood alcohol extracts on the fluorouracil-induced liver injury in mice

作　　者：王灿红 王帅[2] 彭德乾[3] 余章昕 郭鹏[1,2] 魏建和[1,2] WANG Can-hong;WANG Shuai;PENG De-qian;YU Zhang-xin;GUO Peng;WEI Jian-he(Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine ＆ Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization,Hainan Branch Institute of Medicinal Plant,Chinese Academy of Medical Sciences ＆ Peking Union Medical College,Haikou 570311,China;Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,National Engineering Laboratory for Breeding of Endangered Medicinal Materials,Institute of Medicinal Plant Development,Chinese Academy of Medical Science ＆ Peking Union Medical College,Beijing 100193,China;School of Pharmacy,Hainan Medical College,Haikou 571199,China)

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所海南分所海南省南药资源保护与开发重点实验室,海口570311 [2]中国医学科学院北京协和医学院药用植物研究所,北京100193 [3]海南医学院药学院,海口571199

出　　处：《国际药学研究杂志》2018年第3期187-197,共11页Journal of International Pharmaceutical Research

基　　金：海南省重大科技计划资助项目(ZDKJ2016004);海南省自然科学基金资助项目(817290;217291)

摘　　要：目的研究通体沉香醇提物(WTAAE)对氟尿嘧啶(5-FU)所致小鼠肝损伤的保护作用及其机制。方法采用5-FU(25 mg/kg)隔天腹腔注射7次诱导小鼠肝损伤模型,检测小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性和肝组织匀浆液中髓过氧化物酶(MPO)、一氧化氮(NO)、总抗氧化能力(T-AOC)和超氧化物歧化酶(SOD)含量;观察肝组织病理学变化;酶联免疫法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-6的分泌水平;实时定量聚合酶链反应(q PCR)检测肝组织中抗氧化和炎症信号通路基因m RNA的表达。实验中WTAAE为检测样品,野生沉香醇提物(WAAE)与火烙沉香醇提物(FBAAE)为对照。结果与模型组相比,WTAAE能显著降低血清ALT、AST活性,降低肝组织MPO活性和NO含量,升高T-AOC及SOD活性;缓解肝组织的病理损伤程度;降低细胞因子TNF-α、IL-1β和IL-6的分泌水平,上调抗氧化Nrf2-ARE信号通路相关基因m RNA表达,下调炎症NF-κB信号通路相关基因m RNA水平,且WTAAE与WAAE作用相当,优于等药材量的FBAAE。结论 WTAAE对肝损伤有保护作用,其机制与抗氧化应激及抗炎作用有关。Objective To investigate the hepatoprotective effect of whole-tree agarwood-inducing technique-produced agarwood alcohol extract（WTAAE）on liver injury induced by fluorouracil（5-FU）in mice and its mechanism. Methods The mice were injected with 5-FU（25 mg/kg）to establish liver injury model. Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in serum of mice were measured. The myeloperoxidase（MPO）,nitric oxide（NO）,total antioxidant capacity（T-AOC）and superoxide dismutase（SOD）in the liver tissue homogenate were measured,and the degree of liver injury was evaluated by histopathological examination. The secreted levels of tumor necrosis factor α（TNF-α）,interleukin-1β（IL-1β）and IL-6 levels were measured by enzyme-linked immunosorbent assay（ELISA）,and the m RNA expression for the anti-oxidative and inflammatory signaling pathways was detected in liver tissues by real-time polymerase chain reaction（q PCR）. The WTAAE was the test sample and the wild AAE（WAAE）and the fire-burned AAE（FBAAE）were used for comparison in the experiment. Results Compared with the model group,WTAAE significantly decreased ALT and AST activities,reduced MPO and NO levels,and enhanced T-AOC and SOD activity. In addition,WTAAE obviously alleviated the pathological damage degree of liver tissue,decreased the level of secreted cytokines TNF-α,IL-1β and IL-6. Furthermore,WTAAE upregulated the m RNA expression of genes related to the anti-oxidative Nrf2-ARE signaling pathway and downregulated the m RNA expression of genes related to the inflammatory NF-κB signaling pathway. On the whole,the hepatoprotective effect of WTAAE was better than that of FBAAE and similar to that of WAAE. Conclusion WTAAE showed a significant protective effect on the 5-FU induced liver injury in mice,and the mechanism was related to the anti-oxidative stress and anti-inflammatory effect.

关 键 词：通体沉香醇提物 氟尿嘧啶 肝损伤 抗氧化损伤 抗炎 

分 类 号：R575.1[医药卫生—消化系统]