荷叶总生物碱激活肝脏AMPK/Nrf2通路缓解对乙酰氨基酚诱导的小鼠急性肝损伤

Protective effects of total alkaloids from lotus leaf on acetaminophen-induced acute liver injury in mice:roles of activating hepatic AMPK/Nrf2 signaling

为探讨荷叶总生物碱(TAL)对对乙酰氨基酚(APAP)所致小鼠急性肝损伤的保护作用及可能机制,小鼠被随机分为正常组,模型组和TAL低、高剂量组(30、100 mg/kg),连续灌胃给药七天后,除正常组外,其余各组腹腔注射300 mg/kg的APAP诱导急性肝损伤。12小时后,收集各组小鼠的血清与肝脏样本,进行后续实验。结果显示,与模型组相比,TAL可显著降低血清中的ALT和AST活性,下调肝组织中TNF-α、IL-1β、IL-6和MDA含量,上调肝组织中SOD、CAT、GSH-Px和GSH的水平。此外,TAL还明显改善了APAP诱导的小鼠肝组织病变。在TAL的作用下,肝内AMPK磷酸化水平提高,Nrf2蛋白入核,HO-1和GCLC基因表达上调。综上所述,TAL对APAP诱导的急性肝损伤具有保护作用,其机制可能与激活AMPK/Nrf2通路相关。

This study aimed to understand the protective effects of total alkaloids from lotus leaves(TAL)on acute liver injury induced by acetaminophen(APAP)in mice and the potential mechanisms.Mice were randomly divided into 4 groups,i.e.,the normal group,the model group,the TAL low-dosage group(30 mg/kg)and the TAL high-dosage group(100 mg/kg).Animals received TAL through gavage for 7 consecutive days.Then,except the normal group,other groups received APAP(300 mg/kg)by intraperitoneal injection to provoke acute liver injury.Serum and livers of mice were collected 12 h later and subjected to further experiments.Our results showed that as compared to the model group,TAL significantly decreased activities of ALT and AST in the serum and contents of TNF-α,IL-1β,IL-6 and MDA in the liver.In addition,TAL dose-dependently elevated hepatic levels of SOD,CAT,GSH-Px and GSH.Moreover,APAP-induced liver histopathological changes were dramatically alleviated by TAL.Mechanistically,TAL considerably boosted AMPK phosphorylation,induced nuclear translocation of Nrf2 and promoted expression of HO-1 and GCLC.In conclusion,this study revealed that TAL has the capacity of ameliorating APAP-induced acute liver injury,and the underlying mechanisms are related with the activation of hepatic AMPK/Nrf2 cascade.