HBV-ACLF患者外周血和肝脏NK细胞的表达频率及功能与肝损伤的相关性  

Association of the frequency and function of peripheral and liver natural killer cells with liver injury in HBV-ACLF patients

作　　者：邹勇[1,3] 周耀勇[2,3] 宋戈[3] 

机构地区：[1]中山大学附属第三医院输血科,广州510630 [2]中山大学附属第六医院感染科 [3]华中科技大学同济医学院附属同济医院感染免疫研究室,武汉430030

出　　处：《中华微生物学和免疫学杂志》2012年第7期636-641,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学青年基金资助项目（81000180）

摘　　要：目的探讨HBV相关慢加急性肝衰竭（HBV-ACLV）患者外周血和肝组织自然杀伤（NK）细胞的表达频率及功能与肝损伤的相关陛。方法利用多色流式技术检测14例HBV-ACLF患者和15例HBV-CHB（慢性乙型肝炎）患者外周血NK细胞（CD3-CD56＋）的表达频率和NK细胞表面CD10Ta的表达，胞内细胞因子染色技术检测NK细胞分泌IFN-γ的水平。收集20例HBV-ACLF患者、10例轻度CHB患者肝组织穿刺标本，利用免疫组织化学双染技术检测肝组织中CD3和CD57抗原的表达。分析轻度CHB和HBV-ACLF患者肝脏NK细胞的表达频率及与肝损伤程度（TBIL水平）的相关性。结果HBV-ACLF患者与轻度CHB患者外周血NK细胞的表达频率和IFN-γ的表达差异均无统计学意义（12．7％±5．3％vs9．6％±3．3％和4．52％±2．52％vs9．06％±7．6％，P均〉0．05），HBV-ACLF患者外周血CD107a表达（NK细胞的杀伤活性）要显著强于轻度CHB患者（52．1％±18．9％vs30．9％±12．4％，P〈0．05）。HBV-ACLF患者肝组织中CD57＋NK细胞的表达频率显著高于轻度CHB患者（95．1±21．3／低倍镜视野V89．5±10．6／低倍镜视野，P〈0．01）。肝脏CD57＋NK细胞的表达频率与TBIL水平显著正相关，相关系数为0．936。结论外周血NK细胞杀伤活性显著增强和肝脏中CD57＋NK细胞大量募集可能是导致HBV-ACLF免疫性肝损伤加剧，肝细胞大量凋亡和坏死的重要因素。Objective To investigate whether the expression frequency and function of peripheral and liver NK cells was correlated with the liver injury in patients with hepatitis B virus related acute-on-chro- nic liver failure（HBV-ACLF）. Methods Peripheral blood samples were obtained from fifteen HBV-ACLF patients and fifteen chronic hepatitis B patients. The frequency of peripheral NK cells （ CD3- CD56＋ ） and CD107a expression on surface of peripheral NK cells were detected by multicolor flow cytometry. Expression of IFN-γby peripheral NK ceils was detected by intracellular cytokine staining. Needle biopsy liver tissues were obtained from twenty patients with HBV-ACLF, ten patients with mild CHB, and expression of live NK ceils （ CD3-CD57＋ ） was analyzed by dual immmunohistochemical staining of CD 3 and CD57 . Results There was no significant difference in the frequency of peripheral NK cell and IFN-γexpression by peripheral NK cells between HBV-ACLF and mild CHB patients. However, CD107a expression on surface of peripheral NK calls of HBV-ACLF patients was remarkably higher than that of CHB patients. The frequency of hver CD57＋NK cell of HBV-ACLF patients was remarkably higher than that of CHB patients （95.1±21.3/low power field vs 9.5±10.6/low power field, P〈0. 01 ）. Further analysis revealed that the frequency of liver CD57＋ NK cells in HBV-ACLF patients was positively correlated with the TBIL level. Conclusion The en- hanced cytotoxic activity of peripheral NK cells and the recruitment of liver CD57＋ NK cells may aggravate immune-mediated liver injury and promote the apoptosis and necrosis of hepatocytes.

关 键 词：乙型肝炎病毒 肝衰竭 自然杀伤细胞 

分 类 号：R575.3[医药卫生—消化系统]