荷叶总碱对酒精诱导小鼠肝损伤的保护作用

THE PROTECTIVE EFFECTS OF TOTAL ALKALOIDS FROM LOTUS LEAVES ON ALCOHOL-INDUCED LIVER INJURY IN MICE

目的探讨荷叶总碱(TAL)对酒精诱导小鼠肝损伤的保护作用及可能机理。方法将40只小鼠随机分为正常组、肝损伤模型组、TAL低剂量组(30 mg/kg)和TAL高剂量组(100 mg/kg)。每组10只小鼠。造模给药结束后,检测各组小鼠相关生理生化指标(ALT、AST、TG),氧化应激指标(GSH、MDA)和炎症因子指标(TNF-α、IL-1β、IL-6)。采用HE染色法观察各组小鼠肝脏的显微形态。采用免疫印迹与荧光定量PCR法检测各组小鼠肝脏细胞核内的Nrf2蛋白水平与肝脏中Nrf2下游基因的表达水平。结果与正常组相比,模型组小鼠发生肝损伤和肝脏TG积累(P <0.01),肝脏内发生氧化应激和炎症反应(P <0.01),肝脏显微结构明显改变。TAL有效地缓解了这些病变。进一步研究发现,TAL对模型小鼠肝脏中的Nrf2通路具有明显的激活作用。结论 TAL对酒精诱导的小鼠肝损伤具有明显的保护作用。其机制与激活肝脏中Nrf2通路有关。

Objective To investigate protective effects of total alkaloid from lotus leaves(TAL) on alcohol-induced liver injury in mice and possible underlying mechanisms. Methods Forty mice were randomly divided into 4 groups, i.e., normal group, liver injury model group, TAL low dosage group(30 mg/kg) and TAL high dosage group(100 mg/kg). Each group contained 10 mice. After drug treatments, related physiological and biochemical parameters, including alanine transferase(ALT), aspartate transferase(AST) and triglyceride(TG), glutathione(GSH), malondialdehyde(MDA), tumor necrosis factorα(TNF-α), interleukin 1β(IL-1β) and interleukin 6(IL-6), were determined. The micromorphology of the mouse liver was observed after hematoxylin-eosin(HE) staining. NF-E2-related factor-2(Nrf2) protein in the nucleus of liver and expression levels of Nrf2-downstream genes in the liver were analyzed by immunoblotting and quantitative PCR. Results Compared with the normal group, liver injury could be detected in the model group(P<0.01). Considerable TG accumulation, oxidative stresses, and inflammation could be observed in the livers of model mice(P<0.01). These lesions were effectively ameliorated by TAL. Further investigations unveiled that TAL had the capacity of activating Nrf2 pathway in the livers of mice.Conclusion TAL considerably ameliorates alcoholic-induced liver injury in mice. Activation of hepatic Nrf2 pathway is implicated in the liver-protective effects of TAL.