外周血单个核细胞中与慢性乙型肝炎重症化进程有关的免疫分子表达

Study on several immune molecules expressed on peripheral blood mononuclear cells which may play an important role in the aggravation of chronic hepatitis B

目的筛选慢性乙型肝炎（CHB）患者外周血单个核细胞（PBMC）中与肝炎重症化相关的免疫分子。方法采用荧光定量PCR技术检测各型CHB患者PBMC中39个免疫分子（包括白细胞分化抗原、趋化因子受体、凋亡相关配体和受体、黏附分子、Toll样受体等）mRNA的相对表达水平。多组间两两比较采用单因素方差分析中的Scheffe法，相关性检验采用Spearman等级相关分析。结果荧光定量结果显示，39个免疫分子中与肝炎严重程度相关的分子共有9个，即肿瘤坏死因子相关凋亡诱导配体（TRAIL）、TRAIL受体（TRAIL—R）2、CD64、CD30、CD27、CD28、L-选择素（CD62I。）、细胞间黏附分子-1（ICAM-1）和CXC型趋化因子受体（CXCR）2，与健康对照组相比，这9种免疫分子在CHB重度组的表达量增高倍数分别为3．88、4．37、2．51、2．22、2．97、2．53、4．07、4．29和4．25倍（F=1．96、2．13、1．33、1．16、1．57、2．14、2．03、2．10、2．09，均P〈0．05）。其中TRAIL、TRAILR2、CD64、CD30、CD27的表达量与IFN-7的表达量呈显著正相关（r=0．816、0．572、0．462、0．697、0．793，均P〈0．01）。TRAIL-R2、CD64、CD30、CD62L、1CAM-1表达量与TNF-a的表达量呈显著正相关（r=0．494、0．588、0．568、0．968、0．976，均P〈0．01）。结论TRAIL、TRAILR2、CD64、CD30、CD27、CD28、CD62L、ICAM-1和CXCR2的异常表达与肝脏炎性反应和肝炎重症化相关。

Objective To screen immune molecules expressed on peripheral blood mononuclear cells （PBMCs） which are related to the aggravation of chronic hepatitis B （CHB）. Methods Real-time polymerase chain reaction （PCR） was employed to detect the relative expression of 39 immune molecules at mRNA level and then compare the differences between groups （control group, mild CHB group, moderate CHB group and severe CHB group）. The investigated immune molecules included leukocyte differentiation antigens, chemokine receptors, apoptosis-related ligands and receptors, adhesion molecules and Toll like receptors. Scheffe model was used to compare the differences among all groups and Spearman rank correlation was used for correlation analysis. Results Among the 39 immune molecules, the expressions of tumor necrosis factor related apoptosis inducing [igand （TRAIL）, TRAIL receptor （TRAIl=R） 2, CD64, CD30, CD27, CD28, L-selectin （CD62L）, intercellular adhesion molecule-1 （ICAM-1）, chemokine （C-X-C motif） receptor （CXCR） 2 were significantly increased in severe CHB group compared with those in control group （1.96, 2.13, 1.33, 1.16, 1.57, 2.14, 2.03, 2.10 and 2.09, respectively; all P〈0.05）. The expressions of TRAIL,TRAII.-R2, CD64, CD30, CD27 were highly correlated with the expression of interferon gamma （IFN-γ） （r=0.816, 0.572, 0.462, 0.697 and 0.793, respectively; all P^0.01）. The expressions of TRAIL R2, CD64, CD30, CD62L, ICAM-1 were highly correlated with the expression of tumor necrosis factor alpha （TNF -α） （r=0. 494, 0. 588, 0. 568, 0. 968 and 0. 976, respectively; all P〈0. 01）. Conclusion The abnormal expression of TRAIL,TRAIL R2,CD64,CDS0,CD27,CD28,CDf2L, ICAM-1 and CXCR2 may play an important role in the pathogenesis and aggravatoin of hepatitis B.