慢性丙型肝炎患者外周血Cbl-b、CD28和CTLA-4的表达及其临床意义

The expression of Cbl-b,CD28 and CTLA-4 in peripheral blood monouclear cells in patients with chronic hepatitis C

目的探讨慢性丙型肝炎患者外周血E3泛素连接酶Cbl-b及其相关信号分子CD28和CTLA-4的变化规律及其临床意义。方法选择25例慢性丙型肝炎患者和19例健康对照者,分离外周血单个核细胞,应用RT-PCR法检测Cbl-b、CD28和CTLA-4 mRNA相对表达水平;采用荧光定量RT-PCR检测HCV RNA;采用IN-NO-LiPA线性探针杂交法检测HCV基因分型。结果 Cbl-b、CD28和CTLA-4 mRNA在慢性丙型肝炎患者中表达升高,较健康对照分别升高1.38倍、1.90倍和2.68倍,其中CTLA4-4的升高表达具有统计学意义(P<0.05);在HCV1b基因型(n=11)中,Cbl-b和CTLA-4 mRNA水平较HCV 2a基因型(n=14)显著升高,分别升高1.74倍和2.81倍,差异具有统计学意义(P<0.05),而Cbl-b、CD28和CTLA-4水平与HCV RNA和ALT水平均无显著相关性。结论Cbl-b和CTLA-4可能参与了HCV感染所致的机体免疫耐受,在HCV感染慢性化中发挥重要作用。

Objective To investigate the changes and clinical significance of E3 ubiquitin ligase Cbl-b and the related signaling molecules CD28 and CTLA-4 in patients with chronic hepatitis C. Methods 25 patients with chronic hepatitis C and 19 healthy persons were enrolled in this study. Peripheral blood monouclear cells （PBMC）were isolated.The related mRNA expressions of Cbl-b,CD28,and CTLA-4 were measured by RT-PCR; HCV RNA was detected by real-time RT-PCR;Genotyping of HCV was performed using a second generation IN- NO-LiPA line probe assay. Results The mRNA levels of Cbl-b,CD28,and CTLA-4 were increased in chronic hepatitis C, with 1.38-, 1.90-, and 2.68-time higher than those in healthy controls,respectively;The expressions of Cbl-b and CTLA-4 mRNA were significantly increased in HCV genotype lb （n=ll） than those in HCV geno- type 2a （n=14）,with 1.74-and 2.81-time higher,respectively（P〈0.05）;There were no correlations between the lev- els of three molecules and HCV RNA,so as to the associations of those and ALT levels.Conclusion Cbl-b and CTLA-4 may take part in the immune tolerance induced by the HCV infection and play an important role in chronic HCV infection.