槲皮素对对乙酰氨基酚诱导的小鼠急性肝损伤的保护作用

Protective Effect of Quercetin on Acute Liver Injury Induced by Acetaminophen in Mice

目的:探究槲皮素(Quercetin,Que)对对乙酰氨基酚(Acetaminophen,APAP)诱导的小鼠急性肝损伤的保护作用及其机制。方法:将24只雄性C57BL/6J小鼠随机分成3组,每组8只,分别为正常对照组(CON组)、APAP模型组(APAP组,腹腔内注射350 mg/kg APAP溶液)、槲皮素给药组(APAP+Que组,造模2 h后灌胃100 mg/kg槲皮素溶液),APAP处理24 h后进行取材。HE染色法观察各组小鼠肝脏组织病理学变化;用试剂盒测定各组小鼠血清ALT和AST的水平和肝组织GSH的含量;Western blot法测定p-JNK和JNK的表达水平。结果:与CON组相比,APAP组病理学显示大量的炎性细胞浸润,经槲皮素干预后显示肝损伤明显减轻;与APAP组相比,APAP+Que组血清ALT、AST水平均降低(P<0.001),APAP+Que组肝脏组织GSH含量升高(P<0.001);与APAP组相比,Western blot实验结果显示,APAP+Que组小鼠肝脏组织中p-JNK/JNK的比值明显下降。结论:Que对APAP诱导的急性肝损伤具有保护作用,其机制可能与调控凋亡通路JNK的表达水平有关。

Objective:To investigate the protective effect of Quercetin(Que)on acute liver injury induced by Acetaminophen(APAP)and its mechanism.Methods:twenty-four male C57BL/6J mice were randomly divided into 3 groups with 8 mice in each group,which were normal control group(CON group),APAP model group(APAP group)and quercetin administration group(APAP+Que group).The mice in APAP group were intraperitoneally injected with 300 mg/kg APAP.After 2 h of modeling,the mice in APAP+Que group were given by gavage with 400 mg/kg Que solution.After 24 h of APAP treatment,samples were collected.The pathological changes of liver tissue were observed by hematoxylin and eosin(HE)staining.The levels of ALT and AST in serum and the content of GSH in liver tissue were determined by kit.The expression levels of P-JNK and JNK were determined by Western blot.Results:Compared with CON group,APAP group showed a large number of inflammatory cell infiltration,and the liver injury was significantly reduced after quercetin intervention.Compared with APAP group,serum ALT and AST levels were decreased in APAP+Que group(P<0.001),and liver GSH content was increased in APAP+Que group(P<0.001).Compared with the APAP group,Western blot results showed that the p-JNK/JNK ratio in the liver tissues of mice in the APAP+Que group was significantly decreased.Conclusion:Que has a protective effect on APAP-induced acute liver injury,and its mechanism may be related to the regulation of the expression level of apoptotic pathway JNK.