二氢杨梅素对APAP诱导小鼠急性肝损伤的保护作用  

Effect of dihydromyricetin on acetaminophen induced liver injury in mice

作　　者：屠梦珏 魏进歌 陈鑫 王玉琴 TU Meng-jue;WEI Jin-ge;CHEN Xin;WANG Yu-qin(College of Pharmacy,Nantong University,Nantong Jiangsu 226001,China;Dept of Pharmacy,Yancheng First People s Hospital,Yancheng Jiangsu 224005,China)

机构地区：[1]南通大学药学院,江苏南通226001 [2]盐城市第一人民医院药剂科,江苏盐城224005

出　　处：《中国药理学通报》2018年第12期1707-1712,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31500649);南通市科技计划项目(No MS12015101)

摘　　要：目的观察二氢杨梅素(dihydromyricetin,DHM)预防性干预对对乙酰氨基酚(acetaminophen,APAP)诱导的小鼠急性肝损伤的影响及其可能的作用机制。方法采用对乙酰氨基酚诱导的小鼠急性肝损伤模型,预防性给予DHM 1周后,HE染色和生化检测评价小鼠肝脏损伤情况,并检测肝组织谷胱甘肽(GSH)、丙二醛(MDA)水平及超氧化物歧化酶(SOD)活力;活性氧(ROS)荧光探针-DHE染色检测肝组织ROS产生状况;实时定量PCR法检测TNF-α、IL-6、IL-1βmRNA变化;Western blot法检测小鼠肝脏JNK磷酸化水平及Bax蛋白表达水平。结果 DHM能够明显减轻由APAP诱导的小鼠急性肝损伤,升高肝组织GSH水平和SOD活力。实时定量PCR检测发现,DHM预处理明显降低APAP模型小鼠肝组织炎症相关因子mRNA水平;Western blot检测发现,DHM明显降低JNK磷酸化水平及Bax蛋白表达水平。结论 DHM可以通过抗炎和抗氧化应激作用,进而抑制JNK信号通路的激活,并抑制肝细胞凋亡来保护APAP损伤的小鼠肝脏。Aim To observe the effect of dihydromyricetin（DHM） on acetaminophen（APAP） induced liver injury in mice and speculate its possible mechanism. Methods APAP-induced acute liver injury model in mice was used. One week after DHM administration, HE staining and biochemical assay were employed to assess the hepatic injury, and the glutathione（GSH） and malondialdehyde（MDA） levels and superoxide dismutase（SOD） activity in liver tissues.Reactive oxygen species（ROS） fluorescent-DHE staining was used to detect the status of ROS production in liver tissue, real-time quantitative PCR to detect the levels of TNF-α, IL-6 and IL-1β mRNA, and Western blot assay to detect the phosphorylation of JNK in liver and level of Bax protein expression. Results DHM inhibited acute liver injury induced by APAP in mice, and significantly increased the level of GSH and SOD activity in liver tissues. Furthermore, real-time quantitative PCR detection revealed that DHM pretreatment significantly reduced mRNA levels of inflammation related factors in liver of APAP model mice. Western blot analysis revealed that DHM significantly decreased the phosphorylation of JNK and level of Bax protein expression. Conclusion DHM protects APAP induced liver injury by anti-inflammatory, anti-oxidant stress and inhibition of mitochondrial damage-related signaling pathways.

关 键 词：二氢杨梅素 对乙酰氨基酚 肝损伤 氧化应激 炎症 小鼠 

分 类 号：R-332[医药卫生] R284.1