慢加急性肝衰竭小鼠肝组织组蛋白去乙酰化酶mRNA水平变化  

Changes of histone deacetylase mRNA levels after histone acetylation inhibitor management in liver tissue of mice with acute-on-chronic liver failure

作　　者：林列坤 卢春生 周应生 郑义 杨菊红 邹继彬 张仁超 梁旭竞 Lin Liekun;Lu Chunsheng;Zhou Yingsheng(The Center of Medical Genetics and Molecular Diagnosis,Shenzhen Hospital,University of Chinese Academy of Sciences,Shenzhen 518106,Guangdong Province,China)

机构地区：[1]中国科学院大学深圳医院医学遗传与分子诊断中心,广东省深圳市518106 [2]中国科学院大学深圳医院消化内科,广东省深圳市518106 [3]中国科学院大学深圳医院病理科,广东省深圳市518106 [4]中山大学附属第七医院感染病科

出　　处：《实用肝脏病杂志》2021年第3期327-330,共4页Journal of Practical Hepatology

基　　金：深圳市科技计划项目(编号:JCYJ20170307093622283)。

摘　　要：目的探讨组蛋白去乙酰化酶(HDAC)抑制剂干预慢加急性肝衰竭(ACLF)小鼠肝组织组蛋白去乙酰化酶mRNA水平变化。方法随机将小鼠分为7组,每组4只。A组为对照组,B组为模型组,C组为曲古抑菌素A(TSA)处理组,D组为大剂量正丁酸钠处理组,E组为小剂量正丁酸钠处理组,F组为大剂量吡咯烷二硫代氨基甲酸(PDTC)处理组,G组为小剂量PDTC处理组,采用脂多糖联合D-Gal诱导小鼠肝衰竭模型。采用Q-PCR法检测小鼠肝组织Ⅰ类和Ⅱ类HDAC mRNA水平。结果B组肝组织HDAC1mRNA、HDAC2mRNA、HDAC3mRNA和HDAC8mRNA水平分别为(1.7±0.2)、(1.7±0.3)、(1.9±0.6)和(2.6±0.7),而C组、D组、E组、F组和G组均显著降低(P<0.05);B组肝组织HDAC4mRNA、HDAC5mRNA、HDAC6mRNA、HDAC7mRNA、HDAC9mRNA和HDAC10mRNA水平分别为(0.6±0.2)、(6.3±0.9)、(3.4±0.8)、(2.8±1.0)、(6.5±1.1)和(0.4±0.1),而C组、D组、E组、F组和G组均显著降低(P<0.05)。结论HDAC mRNA水平可能与机体乙酰化作用相关,可为应用组蛋白乙酰化调控治疗肝衰竭小鼠提供重要的理论依据。Objective The aim of this study was to study the changes of histone deacetylase mRNA levels after histone acetylation(HDAC)inhibitor intervention in liver tissue of mice with acute-on-chronic liver failure(ACLF).Methods 28 mice were randomly divided into seven group,with four in each,and the liver failure was induced in mice by lipopolysaccharide(LPS)and D-Gal injection.The mice in group A(control),B(model),C,D,E,F and G were intervened by normal saline,normal saline,trichostatin A(TSA),large dose of sodium butyrate,low dose of sodium butyrate,large dose of pyrrolidine dithiocarbarmate(PDTC)and low dose of PDTC,respectively.The hepatic HDAC mRNA was assayed by Q-PCR.Results The hepatic HDAC1mRNA,HDAC2mRNA,HDAC3mRNA and HDAC8mRNA in group B were(1.7±0.2),(1.7±0.3),(1.9±0.6)and(2.6±0.7),while all of them in group C,group D,group E,group F and group G decreased greatly(P<0.05);the hepatic HDAC4mRNA,HDAC5mRNA,HDAC6mRNA,HDAC7mRNA,HDAC9mRNA and HDAC10mRNA in group B were(0.6±0.2),(6.3±0.9),(3.4±0.8),(2.8±1.0),(6.5±1.1)and(0.4±0.1),while all of them in group C,group D,group E,group F and group G decreased significantly as compared to those in group B(P<0.05).Conclusion The hepatic HDAC mRNA levels is related to the acetylation of proteins,which might reinforce the theoretical basis for the application of histone acetylation regulation in Dealing withliver failure in mice.

关 键 词：肝衰竭 组蛋白去乙酰化酶 曲古抑菌素A 正丁酸钠 吡咯烷二硫代氨基甲酸 小鼠 

分 类 号：R575.3[医药卫生—消化系统]