吲哚胺2,3双加氧酶与乙肝病毒不同感染状态T淋巴细胞亚群及病毒载量的相关性研究  

Investigation of the correlation between indoleamine 2,3-dioxygenase and T cell subsets, viral load in different hepatitis B virus infection status

作　　者：曾道炳[1] 卢实春[1] 李军峰[2] 胡冬[2] 周育森[2] 

机构地区：[1]首都医科大学附属北京佑安医院肝胆外科暨肝移植中心,100069 [2]军事医学科学院微生物流行病研究所病原微生物生物安全国家重点实验室

出　　处：《北京医学》2012年第12期1025-1029,共5页Beijing Medical Journal

基　　金：国家自然科学基金(30671977);首都医学发展科研基金(2005-2034)

摘　　要：目的探讨乙肝病毒(HBV)不同感染状态下,吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)表达水平及其与T淋巴细胞亚群及病毒载量的相关性。方法检测受检者外周静脉血IDO mRNA、IDO蛋白、IDO活性,T淋巴细胞亚群及病毒载量(对照组除外);进行各组间均数比较及相关性分析。结果 IDO mRNA、IDO蛋白及IDO活性从高到低依次为急性乙型肝炎组(acute hepatitis B,AHB)、肝硬化组(HBV-related liver cirrhosis,LC)、慢性乙型肝炎组(chronic hepatitis B,CHB)、肝癌组(HBV-related hepatocellularcar cinoma,HCC)、对照组。HCC组及对照组均明显低于其他3组(P<0.01),其余各组间两两比较,差异有统计学意义(P<0.05)。CD3+、CD4+T淋巴细胞在AHB组最高,对照组次之,LC组最低;AHB组、对照组及CHB组均明显高于LC组(P<0.05);AHB组、对照组明显高于HCC组(P<0.05)。CD8+T淋巴细胞在对照组最高,AHB组次之,LC组最低;但仅AHB组、对照组明显高于LC组(P<0.05)。AHB组CD4+/CD8+明显高于其他组(P<0.01)。CHB及LC组病毒载量最高,均明显高于HCC及AHB组(P<0.05)。CD3+、CD4+、CD8+T淋巴细胞与病毒载量、IDO蛋白及IDO活性均呈负相关,CD8+T淋巴细胞与I-DO mRNA呈负相关(r=-0.287,P=0.039);CD4+/CD8+与IDO蛋白及IDO活性均呈正相关(r=0.470,P=0.000;r=0.285,P=0.040),病毒载量与IDO mRNA、IDO蛋白及IDO活性均呈正相关(r=0.530,P=0.001;r=0.416,P=0.002;r=0.649,P=0.000)。结论 HBV感染者IDO表达明显增强,与病毒载量呈正相关,与T淋巴细胞呈负相关,其早期升高有利于病毒清除,但持续升高会导致HBV特异性T淋巴细胞功能抑制,使HBV慢性化。Objective To investigate the expression levels of indoleamine 2,3-dioxygenase（IDO） and the correlation between IDO level, T cell subsets and viral load in hepatitis B related liver disease subjects. Methods Peripheral blood samples were collected, and the the expression level of IDO mRNA and IDO protein in PBMC, IDO activity in serum, T cell subsets, viral load（except the control group） were determined by the relative quantification real time PCR, western blot, HPLC, FCM, absolute quantification real time PCR, respectively. Then these test results were analysed with t test. These data were further analyzed with pearson correlation. Results IDO mRNA, IDO protein level and IDO activity were consis- tent, it meant those of IDO declined in order of acute hepatitis B（AHB）, HBV-related liver cirrhosis（LC）, chronic hepati- tis B （CHB）, HBV-related hepatocellular carcinoma （ HCC）and control group. HCC and control group were significant- ly lower than other groups（P 〈 0.01 ）. Moreover, there were significant differences among other groups （P 〈 0.05）. CD3~ T and CD4~ T cell： AHB group was the highest, then control group, LC group was the lowest. AHB, control and CHB group were higher than LC group significantly （P 〈 0.05）. AHB and control group were also higher than HCC group significantly （P 〈 0.05）. CD8~ T cell： Control group was the highest, then AHB group, LC group was the lowest. Both AHB and control group were significanly higher than LC group （P 〈 0.05）. CD4~/CD8~ in AHB group was higher than others significantly （P 〈 0.01 ）. HBV viral load level in CHB and LC groups were significantly higher than HCC and AHB groups （P 〈 0.05）. Pearson correlation results showed： CD3~ T cell, CD4~ T cell and CD8~ T cell was significantly negatively correlated with viral load, IDO protein level and IDO activity. CD8~ T cell was also significantly negatively correlated with IDO mRNA（r = -0.287, P = 0.039）. CD4~/CD8~ was positively correlated with IDO protein l

关 键 词：吲哚胺2 3双加氧酶 乙型肝炎病毒 T淋巴细胞 

分 类 号：R512.62[医药卫生—内科学]