霍山石斛水提取物通过介导NF-κB/p65和p38MAPK减轻小鼠酒精性肝损伤

摘要

本研究主要探讨霍山石斛水提取物对酒精性肝损伤小鼠的保护作用及其机制.将60只昆明小鼠随机均分成5组,正常组喂饲普通饲料,模型组喂饲普通饲料+52％白酒[12 mL/(kg·bw)]灌胃,低、中、高剂量石斛组喂饲普通饲料+霍山石斛水提取物(1 g/kg、5 g/kg和10 g/kg)灌胃+52％白酒灌胃.40 d后,测肝功能指标(ALT、AST)、氧化应激指标(SOD、MDA)、炎症因子指标(CRP、TNF-α),肝脏做HE染色切片观察,Western blot检测了小鼠肝脏组织中NF-κB/p65和p38 MAPK的磷酸化水平.切片可见,中、高剂量石斛组肝脏组织损伤情况较模型组明显减轻.中、高剂量石斛组较模型组SOD升高(P＜0.01),ALT、AST、MDA、CRP和TNF-α降低(P＜0.01).高剂量霍山石斛水提取物可显著抑制酒精性肝损伤诱导的NF-κB/p65和p38 MAPK的磷酸化水平升高.结果表明,霍山石斛水提取物可降低酒精对肝细胞的损伤作用,其作用机制可能是通过介导NF-κB/p65和p38 MAPK发挥抗氧化、抗炎作用来实现的.%Alcoholic hepatic injury is caused by the toxicity of long-term drinking attracts more and more attention in recent years.Increasing studies have shown that a variety of bioactive ingredients in Dendrobium huoshanense C.Z.Tang et S.J.Cheng(DHC) possessed protective effect on alcoholic liver damage.In present study,the protective effect of DHC on alcoholic liver damage was evaluated and the possible underlying mechanism was explored.This study aimed to provide a reliable theoretical basis for the domain of protecting liver for DHC.The hepatoprotective effects of DHC in a mouse model of acute alcohol-induced liver injury were evaluated based on biochemical indicators and antioxidative capacity of serum and liver in 40 d.Severe liver damage caused by 52％ ethanol intake with increasing activation of hepatic markers was decreased in the group of mice fed DHC,and the results were confirmed through hematoxylin and eosin staining.Serum biochemical indicators and antioxidative capacity were abnormal by intragastric administration of 52％ ethanol,but recovered by DHC.Fttrthermore,DHC increased the activity of antioxidant enzymes and reduced inflammatory reactions in liver.The experimental results indicate that DHC had prevcntive and therapeutic effects against acute alcohol-induced liver injury because it could get down the levels of ALT,AST,CRP,TNFα,MDA,and make up the levels of SOD.DHC treatment significantly decreased the relative levels of NF-κB/p65 and the phosphorylation of p38 MAPK.Therefore,the liver effects of DHC may be attributed to its antioxidant and anti-in? ammatory activities,NF-κB/p65 and p38 MAPK may be play important roles in response to acute liver injury and are involved in the inflammatory response and oxidative injury