摘要
目的研究槲皮素对雷公藤甲素致小鼠免疫性肝损伤的保护作用,并探索该作用与核因子E2相关因子/抗氧化应答元件(Nrf2/ARE)信号通路的相关性。方法 50只C57BL/6J小鼠随机分为对照组、模型组、(20、50、80)mg/kg槲皮素预处理组,每组10只,槲皮素预处理组每日上述不同剂量的槲皮素1次,连续10 d。实验末期,除正常组外其余各组小鼠灌胃给予雷公藤甲素(500μg/kg)建立免疫性肝损伤模型,22 h后测定小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)表达水平、肝组织谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平、HE染色观察肝脏组织病理改变、实时定量PCR检测血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO1)、谷氨酰半脱氨酸连接酶催化亚单位(GCLC)表达量、Western blot法检测细胞核内Nrf2表达水平。结果与模型组相比,槲皮素高剂量组可以明显降低小鼠血清ALT、AST水平,下调肝组织MDA表达水平并提高GSH、SOD含量,明显改善肝组织病理损伤情况,且高剂量槲皮素组可显著诱导Nrf2转位入核,其下游相关基因HO-1、NQO1、GCLC的表达量也显著上升。中剂量槲皮素组具有一定的保护作用,低剂量槲皮素组效果不明显。结论高剂量槲皮素可保护雷公藤甲素引起的免疫性肝损伤,并且该保护作用与激活抗氧化应激Nrf2/ARE信号通路有关。
Objective To observe the protective effect of quercetin against immunological liver injury induced by triptolide,and investigate the involvement of Nrf2/ARE signaling pathway in the protection. Methods Fifty C57BL/6J mice were randomly divided into five groups： control group,model group,（20,50,80） mg/kg quercetin pre-treatment groups. Each group included 10 mice. The mice were treated with different doses of quercetin once daily for consecutive 10 days. At the end of the experiment,triptolide（500 μg/kg） was given intragastrically to induce immunological liver injury in all groups except for the control group. Twenty-two hours later,the levels of serum ALT,AST were detected. The contents of GSH,SOD and MDA in liver tissue homogenates were measured through commercial kits. HE staining was performed to observe pathologic changes of the liver. The mRNA expressions of heme oxygenase-1（HO-1）,NQO1,glutamate-cysteine ligase catalytic subunit（GCLC） was tested by quantitative real-time PCR,and the protein expression of Nrf2 was detected by Western blotting. Results Compared with the model group,the serum activities of ALT and AST as well as MDA content remarkably decreased by the administration of quercetin（80 mg/kg）,while GSH,SOD contents were elevated in liver tissues; pathologic changes of the liver was ameliorated evidently by quercetin; Nrf2 protein expression in the nucleus as well as mRNA expressions of HO-1,NQO1,GCLC increased. Moreover,the protective effect of 50 mg/kg quercetin was not as good as that of 80 mg/kg quercetin,and 20 mg/kg quercetin did little against the immunological liver injury. Conclusion High-dose quercetin can inhibit immunological liver injury induced by triptolide,and the mechanism may be associated with the activation of Nrf2/ARE signaling pathway.
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2017年第3期300-304,共5页
Chinese Journal of Cellular and Molecular Immunology
基金
重庆市基础与前沿研究项目(cstc2014jcyjA10108)
中央高校基本业务费(CQDXWL-2014-Z007,201310611045)
