白藜芦醇通过AMPK/PPARα/PGC1α影响酒精依赖致肝损伤机制研究  

Study on the mechanism of resveratrol affecting the repair of alcohol-dependent liver injury through AMPK/PPARα/PGC1α

作　　者：郑天翼 韩智学[1] 薛继婷[1] 徐晓焱[1] 张杰[1] 刘洪凤[1] 杨勇[1] 岳辉[1] ZHENG Tian-yi(Mudanjiang Medical University,Mudanjiang 157011,Heilongjiang,China)

机构地区：[1]牡丹江医学院,黑龙江牡丹江157011

出　　处：《牡丹江医学院学报》2024年第1期1-4,58,共5页Journal of Mudanjiang Medical University

基　　金：黑龙江省自然科学基金项目(LH2020H075);黑龙江省省属高等学校基本科研业务费科研项目(2022-KYYWF-0706);黑龙江省卫生健康委科技计划项目(20220202020597);牡丹江医学院导师科研专项计划项目(YJSZX2022035,YJSZX2022030)。

摘　　要：目的 观察白藜芦醇(Resveratrol, RES)对酒精依赖大鼠肝组织损伤以及AMP依赖的蛋白激酶(adenosine 5-monophosphate-activated protein, AMPK)/过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptorα,PPARα)/过氧化物酶体增殖物激活受体γ辅激活子1α(peroxisome proliferator activated receptor gamma coactivator 1 alpha, PGC1α)信号通路的影响,讨论RES治疗酒精依赖致肝损伤的修复机制,为临床应用RES提供科学依据。方法 将SPF级雄性大鼠采用随机数字表法设立空白对照组、酒精依赖模型组,采用双瓶自由饮建立20%的酒精依赖模型;酒精依赖模型组制备成功后随机分为酒精依赖模型组、RES高、中、低剂量治疗组,继续给与双瓶自由饮,RES按照100、50、25 mg/(kg·d)剂量灌胃14 d。建模期间检测大鼠体重、饮酒量和饮水量,RES治疗后蛋白免疫印迹法检测大鼠肝组织AMPK、磷酸化AMP依赖的蛋白激酶(phosphorylation-adenosine 5’-monophosphate-activated protein kinas, p-AMPK)、PPARα和PGC1α蛋白表达。结果 蛋白免疫印迹法结果显示:与空白对照组比较,酒精依赖模型组p-AMPK(t=6.61,P<0.05)、PPARα(t=3.08,P<0.05)和PGC1α(t=7.09,P<0.05)表达水平显著下调;与酒精依赖模型组比较,RES高剂量治疗组p-AMPK(F=8.60,P<0.05)、PPARα(F=4.38,P<0.05)和PGC1α(F=11.33,P<0.05)显著上调。结论 结果显示RES可能通过调控AMPK/PPARα/PGC1α信号发挥保护作用。Objective To observe the effects of resveratrol(RES)on liver tissue injury and AMP-dependent protein kinase(Adenosine 5'-monophosphate-activated protein(AMPK)/peroxisome proliferator-activated receptor alpha(PPARα)/peroxisome proliferator-activated receptor 1 alpha(PPARα)in alcohol-dependent rats.To discuss the repair mechanism of alcohol dependence-induced liver injury by RES,and to provide a scientific basis for the clinical application of RES.Methods SPF-grade male rats were set up as blank control group and alcohol dependence model group by randomized numerical table method,and double bottles of free drinking established a 20%alcohol dependence model.The alcohol dependence model group was randomly divided into the alcohol dependence model group,the RES high,medium,and low dosage treatment group after successful preparation of the alcohol dependence model group,and continued to be given double bottles of free drinking.RES was administered according to the dosage of 100,50,and 25 mg/(kg·d)by gavage for 14 days.During the modeling period,the body weight,alcohol consumption,and water intake were detected,and the protein expression of AMPK,p-AMPK,PPARα,and PGC1αin rat liver tissue was detected by protein immunoblotting after RES treatment.Results Protein immunoblotting showed that the expression levels of p-AMPK(t=6.61,P<0.05),PPARα(t=3.08,P<0.05),and PGC1α(t=7.09,P<0.05)were significantly down-regulated in the alcohol dependence model group compared to the blank control group(P<0.05).RES high-dose treatment group compared to the alcohol dependence model group AMPK,p-AMPK(F=8.60,P<0.05),PPARα(F=4.38,P<0.05)and PGC1α(F=11.33,P<0.05)were significantly up-regulated(P<0.05).Conclusion RES was able to alleviate liver injury in alcohol-dependent rats,and the mechanism may be related to the protective effect through the regulation of the AMPK/PPARα/PGC1αsignaling pathway.

关 键 词：白藜芦醇 酒精依赖 AMPK PPARΑ PGC1α 

分 类 号：R285.5[医药卫生—中药学]