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目的探讨干扰素治疗对慢性乙型肝炎惠者外周血树突状细胞(DC)表型的影响,及其疗效与外周血DC表型的关系。方法分别采集23例慢性乙型肝炎(CHB)患者干扰素治疗前和治疗满4mo时的抗凝外周静脉血,并以8例正常健康人作为对照,分离外周血单个核细胞进行体外培养,在重组人白细胞介素4和重组人拉细胞-巨噬细胞集落刺激因子的作用下使DC增殖、成熟,以间接免疫荧光流式细胞技术检测DC表型。结果 干扰素治疗4mo时DC的增殖水平较治疗前显著提高,在相同培养条件下,细胞总量平均增加2.8倍;惠者DC表面CD80表达水平在治疗前和治疗后与健康对照组未见显著差异,而CD86,HLA-DR和ICAM-1的表达在治疗前均显著低于健康对照组(分别为p<0.05,p<0.001和p<0.01),治疗后DC表面CD86,HLA-DR和ICAM-1的表达较治疗前均显著增加(分别为p<0.05,p<0.05和p<0.01),而与健康对照未见显著差异;进一步分析发现,干扰素完全应答组除CD80以外,DC表面CD86,HLA-DR和ICAM-1的表达均相应高于部分应答和无应答组,且治疗后这四种分子与无应答组之间的并具有显著性意义(分别为p<0.05,p<0.01,p<0.01和p<0.05)。结论CHB患者外周血DC不成熟,功能低下,并可能影响干扰素的抗病素疗效;干扰素治疗可显著提高DC的增殖和成熟,进而促进机体清除乙肝病毒。
Objective To investigate the effect of interferon treatment on the phenotype of dendritic cells (DCs) in peripheral blood of patients with chronic hepatitis B and its relationship with the phenotype of peripheral blood DC. Methods Peripheral blood mononuclear cells (PBMCs) were collected from 23 patients with chronic hepatitis B (CHB) before anticoagulation and 4 months after treatment, respectively. Eight normal healthy individuals were used as controls. Peripheral blood mononuclear cells Recombinant human interleukin-4 and recombinant human pulsed macrophage colony-stimulating factor were used to proliferate and mature DCs. DC phenotype was detected by indirect immunofluorescence flow cytometry. Results The proliferation of DC at 4mo was significantly higher than that before treatment. Under the same culture conditions, the total cell number increased by 2.8 times on average. The expression of CD80 on DC surface was not significantly different from that before treatment and after treatment While the expression of CD86, HLA-DR and ICAM-1 were significantly lower than those of the healthy control group before treatment (p <0.05, p <0.001 and p <0.01, respectively) The expression of ICAM-1 was significantly increased (p <0.05, p <0.05 and p <0.01, respectively) compared with that before treatment, but not significantly different from that of healthy controls. Further analysis showed that, in addition to CD80, The expression of CD86, HLA-DR and ICAM-1 on the surface were higher than those on the part of the response and non-response groups, and there was significant difference between the four molecules and the non-response group after treatment (p <0.05, p <0.01, p <0.01 and p <0.05). Conclusions The peripheral blood DC of CHB patients are immature and have low function, which may affect the curative effect of interferon. The treatment with interferon can significantly increase the proliferation and maturation of DC, and then promote the clearance of hepatitis B virus.