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

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。

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

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.