摘要
目的研究异绿原酸B(ICAB)对四氯化碳(CCl4)致小鼠急性肝损伤的保护作用。方法建立CCl4诱导小鼠急性肝损伤实验模型并评价ICAB的保护作用,测定小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)水平和肝组织丙二醛(MDA)含量,以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性。采用HE染色对肝组织细胞形态进行观察;Western印迹法测定ICAB对肝损伤小鼠肝细胞中核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)和醌氧化物还原酶1(NQO1)表达的影响。结果 ICAB各给药组(5、10和20 mg/kg)均可不同程度抑制CCl4所致小鼠血清ALT、AST和MDA的升高(P<0.01),ICAB高剂量组(20 mg/kg)明显提高肝细胞中SOD(P<0.01)和GSH-Px活性水平(P<0.05),降低MDA含量。同时,ICAB能改善CCl4造成的肝组织病理学损伤。此外,ICAB可促进Nrf2的表达及Nrf2的核转位,进而促进Nrf2下游靶蛋白HO-1和NQO1的表达。结论 ICAB对CCl4引起的小鼠急性肝损伤具有明显的保肝降酶作用,其作用机制可能与参与调节Nrf2信号通路、缓解氧化应激相关。
Objective To investigate the effect of isochlorogenic acid B（ICAB）on CCl4-induced acute liver injury（ALI）in mice. Methods The animal model of CCl4-induced ALI in mice was established and then the protective effect of ICAB was evaluated using this model. Serum levels of alanine transaminase（ALT）and aspartate aminotransferase（AST）,hepatic levels of malondialdehyde（MDA）and the activities of superoxide dismutase（SOD）and glutathione peroxidase（GSH-Px）were measured by spectrophotometric methods. Liver cell morphology was observed by hematoxylin and eosin staining method and the effects of ICAB on the protein expression of nuclear factor erythroid-2-related factor 2（Nrf2）,heme oxygenase-1（HO-1）and quinone oxidoreductase 1（NQO1）in mice hepatocyte were determined by Western blot method. Results ICAB（5,10 and 20 mg/kg）significantly protected against CCl4-induced liver injury by reducing the elevated levels of serum aminotransferases and hepatic MDA and remarkably restored the impaired antioxidants. Meanwhile,the histopathological changes were also attenuated in mice. In addition,ICAB could induce the protein expression of Nrf2 and promote its nuclear translocation,and further increase the protein expression of HO-1 and NQO1. Conclusion ICAB has protective effect against CCl4-induced ALI in mice,which is mainly due to its ability to promote the nuclear translocation of Nrf2 and decrease the oxidative stress.
作者
刘鑫
徐小薇
LIU Xin XU Xiao-wei(Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China)
出处
《国际药学研究杂志》
CSCD
北大核心
2017年第6期531-536,共6页
Journal of International Pharmaceutical Research
