miRNA-548ah调控HDAC4影响HBV复制和表达及临床意义  

Effect and clinical significance of miRNA-548ah regulation of HDAC4 in the replication and expression of hepatitis B virus

作　　者：王蔚[1,2] 赵伟[3] 邢同京[4] 肖丽 咸建春[1] 尹有美[1] WANG Wei;ZHAO Wei;XING Tong-jing;XIAO Li;XIAN Jian-chun;YIN You-mei(Taizhou People＇s Hospital,Taizhou,Jiangsu 225300,China)

机构地区：[1]泰州市人民医院感染科,江苏泰州225300 [2]东南大学医学院,江苏南京210009 [3]东南大学附属第二医院感染科,江苏南京210003 [4]温州医科大学附属台州医院感染科,浙江临海317000

出　　处：《中华医院感染学杂志》2018年第16期2401-2405,2410,共6页Chinese Journal of Nosocomiology

基　　金：国家自然科学基金资助项目(81571997)

摘　　要：目的探讨微小RNA-548ah(miRNA-548ah)调控组蛋白去乙酰化酶4(HDAC4)对乙型肝炎病毒(hepatitis B virus,HBV)复制和表达的影响及其在肝组织中的表达与相关性。方法选择2015年-2017年泰州市人民医院诊治的慢性HBV感染患者18例为研究对象,其中慢性乙型肝炎(Chronic hepatitis B,CHB)患者9例,乙型肝炎肝硬化(LC)患者9例,荧光定量PCR检测三种不同肝癌细胞株及CHB患者肝组织中miRNA-548ah和HDAC4分子的表达,应用miRNA-548ah模拟剂和抑制剂转染Huh7细胞、HepG2细胞和HepG2,2,15细胞,检测细胞培养上清中HBsAg、HBeAg、HBV DNA的表达水平;Pearson相关分析CHB患者肝组织中miRNA548ah和HDAC4表达与临床指标的相关性。结果 miRNA-548ah和HDAC4在Huh7细胞、HepG2细胞和HepG2,2,15细胞的表达差异具有统计学意义(P<0.001);转染pHBV1.3质粒的HepG2细胞、Huh7细胞、HepG2,2,15细胞中,与对照组比较,miRNA-548ah模拟剂组HBsAg、HBeAg和HBV DNA的表达均升高,miRNA-548ah抑制剂组HBsAg、HBeAg和HBV DNA表达均降低(P<0.001);CHB患者肝组织中miRNA548ah的表达为(0.90±0.56),低于乙肝LC患者的表达(1.62±0.71)(P<0.05);CHB患者肝组织中miRNA548ah和HDAC4的表达呈负相关(r=-0.746,P=0.021),肝组织中HDAC4的表达水平与血清ALT的水平呈正相关(r=0.733,P=0.025)。结论 miRNA-548ah可通过靶向HDAC4调控乙型肝炎病毒的复制与表达,并且影响CHB的病情进展。OBJECTIVE To investigate the effect and clinical significance of miRNA-548 ah regulation of HDAC4 in the replication and expression of hepatitis B virus,as well as the expression and correlation of miRNA-548 aand HDAC4 in liver tissue.METHODS A total of 18 cases of patients with chronic HBV infection diagnosed and treated in Taizhou People′s Hospital during 2015 to 2017 were included as subjects,in which 9 were chronic hepatitis B（CHB）patients,9 were cirrhosis related hepatitis B patients.Expression levels of miRNA-548 ah and HDAC4 in Huh7 cells,HepG2 cells,HepG2.2.2.15 cells and liver tissue of chronic hepatitis B patients were detected by fluorescent quantitative polymerase chain reaction.Huh7,HepG2 and HepG2.2.2.15 cells were transfected by mimics and inhibitors of miRNA-548 ah.The levels of hepatitis Be antigen（HBeAg）,hepatitis B surface antigen（HBsAg）and HBV DNA in the culture supernatant were detected.Pearson correlation analysis was used to study the correlation between expression of miRNA548 ah and HDAC4 and clinical indexes in liver tissue of chronic hepatitis B patients.RESULTS The expression levels of miRNA-548 ah and HDAC4 in Huh7 cells,HepG2 cells and HepG2,2,15 cells were significantly different（P〈0.001）.In HepG2,Huh7 and HepG2,2,15 cells transfected with pHBV1.3 plasmid,the expression levels of HBsAg,HBeAg and HBV DNA were significantly increased in the miRNA-548 ah mimics group compared with the control group,whereas the expressiom levels of HBsAg,HBeAg and HBV DNA in the miRNA-548 ah inhibitor group were significantly decreased（P〈0.001）.The expression of miRNA548 ah in liver tissues of patients with chronic hepatitis B was（0.90±0.56）,significantly lower than that of patients with cirrhosis related hepatitis B virus（1.62±0.71）（P〈0.05）.There was a significant negative correlation between the expression levels of miRNA548 ah and HDAC4 in the liver tissues of patients with chronic hepatitis B（r=-0.746,P=0.021）.The expression of HDAC4 in liver tissue was p

关 键 词：miRNA-548ah HDAC4 乙型肝炎 慢性 

分 类 号：R512.62[医药卫生—内科学]