片仔癀对酒精诱导的急性肝损伤小鼠自噬和NLRP3炎症小体活化的影响  

Effects of Pien-Tze-Huang on autophagy and activation of NLRP3 inflammasome in mice with alcohol-induced acute liver injury

作　　者：许赞术 谭耀龙 张庆 黄贞伟 郑燕芳[3] 黄鸣清[3] XU Zanshu;TAN Yaolong;ZHANG Qing;HUANG Zhenwei;ZHENG Yanfang;HUANG Mingqing(Nanjie Community Health Service Center of Gulou District,Fuzhou 350001,China;The First Affiliated Dongguan Hospital of Guangdong Medical University,Dongguan 523121,China;Fujian University of Traditional Chinese Medicine,Fujian 350122,China)

机构地区：[1]福州市鼓楼区南街街道社区卫生服务中心,福建福州350001 [2]广东医科大学附属东莞第一医院,广东东莞523121 [3]福建中医药大学药学院,福建福州350122

出　　处：《药学研究》2023年第8期537-542,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.81973437、82274080);福厦泉国家自主创新示范区协同创新平台专项(No.2021FX02)。

摘　　要：目的研究片仔癀(PTH)对酒精诱导小鼠急性肝损伤的保护作用及可能机制。方法将C57BL/6小鼠随机分为空白组、酒精组、PTH低(75 mg·kg^(-1))、中(150 mg·kg^(-1))、高(300 mg·kg^(-1))剂量组,连续灌胃给药3 d(2次/天)。除空白组外,其余各组小鼠于末次给药2 h后灌胃酒精(0.12 mg/10 g)进行造模;24 h后各组小鼠摘眼球取血以测定ALT、AST和TG水平;并取肝组织进行HE检查;qRT-PCR检测肝组织中IL-6、IL^(-1)β和TNF-αmRNA表达水平;Western blot检测NLRP3、Caspase-1 p20、IL^(-1)8、Beclin1、LC3蛋白表达水平。结果与模型组相比,PTH可明显减轻酒精诱导的小鼠急性肝损伤病理情况,降低血清中ALT、AST和TG的含量(P<0.05或P<0.01);PTH可明显降低酒精诱导的急性肝损伤小鼠肝组织中IL-6、IL^(-1)β和TNF-αmRNA的表达水平(P<0.05或P<0.01);PTH可明显上调酒精诱导急性肝损伤小鼠肝组织中LC3-Ⅱ/LC3-Ⅰ比值以及Beclin1的蛋白表达水平(P<0.05或P<0.01),下调NLRP3、Caspase-1 p20、IL^(-1)8蛋白表达水平(P<0.05或P<0.01)。结论片仔癀可能通过调控自噬和NLRP3炎症小体活化而减少炎症介质释放,进而改善酒精诱导的小鼠急性肝损伤。Objective To study the protective effect and possible mechanism of Pien-Tze-Huang(PTH)on acute mice liver injury induced by alcohol.Methods C57BL/6 mice were randomly divided into control group,alcohol group,low-dose(75 mg·kg^(-1)),medium-dose(150 mg·kg^(-1))and high-dose PTH group(300 mg·kg^(-1)),and then the mice were intragastrically administered with PTH for 3 days(twice a day).In order to establish acute liver injury model,mice(except control group)were intragastrically administered with alcohol(0.12 mL/10 g)2 h after the last administration.After 24 hours,eyeball blood was collected to determinate the levels of ALT,AST and TG.Liver tissue was taken for HE examination.mRNA expression levels of IL-6,IL^(-1)βand TNF-αin liver tissues were detected by qRT-PCR.The protein expression levels of NLRP3,Caspase-1 p20,IL^(-1)8,LC3 and Beclin1 were also detected by Western blot.Results Compared with model group,PTH could significantly reduce the pathological condition of alcohol-induced acute mice liver injury,and reduce the contents of ALT,AST and TG in serum(P<0.05 or P<0.01).PTH sharply decreased the mRNA expression levels of IL-6,IL^(-1)βand TNF-αin mice liver tissue(P<0.05 or P<0.01).PTH could dramatically up-regulate the ratio of LC3-Ⅱ/LC3-Ⅰand protein expression of Beclin1 in mice liver tissue(P<0.05 or P<0.01).PTH could down-regulate protein expression levels of NLRP3,Caspase-1 p20,IL^(-1)8 in mice liver tissue(P<0.05 or P<0.01).Conclusion PTH may reduce the release of inflammatory mediators by regulating autophagy and activation of NLRP3 inflammasome,therefore improving alcohol-induced acute liver injury in mice.

关 键 词：片仔癀 急性肝损伤 炎症反应 NLRP3炎症小体 自噬 

分 类 号：R285.5[医药卫生—中药学]