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.
作者
王灿红
王帅
彭德乾
余章昕
郭鹏
魏建和
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)
出处
《国际药学研究杂志》
CAS
CSCD
北大核心
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)
关键词
通体沉香醇提物
氟尿嘧啶
肝损伤
抗氧化损伤
抗炎
whole-tree agarwood-indueing technique-produced agarwood alcohol extracts
fluorouracil
liver injury
anti-oxidation
anti-inflammation
