慢性乙型肝炎患者外周血外泌体HBV-miR-3与现有病毒学指标的关系  

The relationship between serum exosome HBV-miR-3 and current viral markers in CHB patients

作　　者：淦伟强[1] 陈希 朱翔[1] 崔毅峙 刘静[1] 王通 高志良[1] GAN Wei-qiang;CHEN Xi;ZHU Xiang;CUI Yi-zhi;LIU Jing;WANG Tong;GAO Zhi-liang(Department of Infectious Diseases,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510630;Institute of Life and Health Engineering,Jinan University,Guangzhou,Guangdong 510632,China)

机构地区：[1]中山大学附属第三医院感染科,广东广州510630 [2]暨南大学生命科学技术学院/生命与健康工程研究院,广东广州510632

出　　处：《热带医学杂志》2020年第9期1121-1126,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81672701,81700527);十三五国家科技重大专项(2018ZX10302204-002)。

摘　　要：目的检测慢性乙型肝炎(CHB)患者外周血外泌体中是否存在乙型肝炎病毒(HBV)-miR-3表达及其与生化学、现有病毒学指标之间的相关性。方法收集2016年9月-2017年3月在中山大学附属第三医院感染科门诊就诊的无抗病毒治疗的CHB患者外周血血清48份,健康对照者、丙型肝炎病毒(HCV)感染者、脂肪肝患者血清各12份,提取血清外泌体并检测HBV-miR-3滴度。同时检测患者外周血乙型肝炎表面抗原(HBsAg)、前基因组RNA(pgRNA)等指标。分析CHB患者HBV-miR-3与现有病毒学指标的关系。结果 HBV-miR-3仅在CHB患者中检出,浓度为(6.41±3.55)log10 copies/mL,在健康对照者、丙型肝炎患者及脂肪肝患者外周血外泌体中均未检出。HBV miR-3与丙氨酸氨基转移酶无明显相关性(R2=0.047,P>0.05),与HBV DNA、pgRNA、HBsAg呈正相关(R2=0.311、0.336、0.811,P均<0.05),其中与HBsAg高度相关。e抗原阳性患者HBV-miR-3滴度显著高于e抗原阴性患者[(5.88±2.03)log10 copies/mL vs.(2.38±1.96)log10 copies/mL,P<0.05)]。在HBV DNA高病毒载量组、中病毒载量组、低病毒载量组和阴性组中HBV-miR-3定量分别为(9.09±1.08)、(6.08±2.19)、(5.24±4.23)和(4.55±3.96)log10 copies/mL,两两比较,高病毒载量组miR-3定量显著高于其他组别(P<0.05),其他三组之间差异无统计学意义(P>0.05)。结论 HBV-miR-3可在CHB患者外周血血清外泌体中检测到。在无抗病毒治疗CHB患者中,HBV-miR-3与HBsAg、HBV DNA、pgRNA呈正相关,其中与HBsAg高度相关。Objective To detect the expression of hepatitis B virus(HBV)-miR-3 in peripheral blood exosomes of chronic hepatitis B(CHB) patients and study its correlation with biochemical and viral markers.Methods Serum samples were collected from 48 CHB patients without antiviral treatments,12 healthy controls,12 hepatitis C patients and 12 fatty liver disease patients.Serum exosomes were extracted and HBV-miR-3 titers were detected.Hepatitis B surface antigen(HBsAg),pregenomic RNA(pgRNA) and other viral markers were also detected.The relationships between HBV-miR-3 and current viral markers were analyzed.Results HBV-miR-3 was only detected in peripheral blood exosomes of CHB patients with a concentration of(6.41±3.55) log10 copies/mL,but not detected in the peripheral blood exosomes of healthy controls,hepatitis C patients and fatty liver disease patients.HBV-miR-3 was not correlated with ALT level,but was positively correlated with HBV DNA,pgRNA and HBsAg.It was highly correlated with HBsAg and the correlation coefficient was0.811.The titer of HBV-miR-3 in e antigen positive patients was significantly higher than that in e antigen negative patients[(5.88±2.03) log10 copies/mL vs.(2.38±1.96) log10 copies/mL,P<0.05)].HBV-miR-3 contents in the HBV DNA high viral load group,medium viral load group,low viral load group and undetectable group were(9.09±1.08),(6.08±2.19),(5.24±4.23) and(4.55±3.96) log10 copies/mL,respectively.HBV-miR-3 in high viral load group were significantly higher than those in the other three groups(P<0.05).HBV pgRNA in the HBV DNA high viral load group,medium viral load group,low viral load group and undetectable group were(6.38±1.11),(2.86±1.63),(1.64±1.89) and(2.28±2.34)log10 copies/mL,respectively.HBV pgRNA in high viral load group were significantly higher than those in the other three groups(P<0.05).Conclusion HBV-miR-3 could be detected in serum exosomes of C.HB patients.HBV-miR-3 was positively correlated with HBsAg,HBV DNA and pgRNA in CHB patients without antiviral experience,and was h

关 键 词：乙型肝炎 病毒标记物 外泌体 MICRORNA pgRNA 

分 类 号：R512.62[医药卫生—内科学]