【摘要】：目的探討兩種給藥方案對慢性HBV感染者外周血中T淋巴細(xì)胞表面PD-1及其主要配體PDL1的影響,以及其與血清HBV-DNA的關(guān)系。方法 71例慢性HBV感染者按HBV-DNA載量不同分為3lg IU/m L、3~6 lg IU/m L和6 lg IU/m L 3組,進(jìn)入療程后按照給藥不同分為:拉米夫定組(LAM組)23例,拉米夫定+阿德福韋酯聯(lián)合治療組(LAM+ADV組)48例,分別于治療的0、12和24周時(shí),采用流式細(xì)胞儀檢測患者外周血中CD4+和CD8+T細(xì)胞表面PD-1、PD-L1的表達(dá),ELISA法檢測外周血中γ-干擾素(IFN-γ)的表達(dá),同時(shí)檢測HBV-DNA、肝功能、HBV血清學(xué)標(biāo)志物等,并設(shè)立正常對照組26例。結(jié)果不同HBV-DNA載量患者的外周血中CD4+和CD8+T細(xì)胞表面PD-1、PD-L1的表達(dá)均明顯高于正常對照組(P0.05),且與HBV-DNA載量呈正相關(guān)(P0.05),而IFN-γ水平均明顯低于正常對照組(P0.05);抗病毒治療后,兩種治療方案組患者的PD-1、PD-L1表達(dá)均有明顯下降,除LAM組的CD4+PD-L1+外其他CD4+和CD8+T細(xì)胞表面的PD-1、PD-L1在治療前與治療12周和治療24周均差異有統(tǒng)計(jì)學(xué)意義(P0.05),其中LAM+ADV組在降低的速度和幅度上均明顯優(yōu)于LAM組(P0.05);IFN-γ的表達(dá)逐漸升高,至治療24周時(shí)升至(24.55±5.81)pg/m L,明顯高于治療前(13.97±4.13)pg/m L(P0.05),但兩治療組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論慢性乙型肝炎患者外周血中CD4+和CD8+T細(xì)胞表面PD-1、PD-L1的表達(dá)與HBV-DNA載量呈正相關(guān),抑制HBV的復(fù)制可以有效地降低負(fù)性調(diào)控因子PD-1、PD-L1的表達(dá);LAM+ADV聯(lián)合治療方案對PD-1、PD-L1降低的速度和幅度明顯優(yōu)于LAM的單一用藥,更易提高T淋巴細(xì)胞的活性。
[Abstract]:Objective to investigate the effects of two administration regimens on PD-1 on T lymphocyte surface and its main ligand PDL1 in peripheral blood of patients with chronic HBV infection and the relationship between them and serum HBV-DNA. Methods Seventy-one patients with chronic HBV infection were divided into three groups according to their HBV-DNA load: 3lg IU/m L 3L 6 LG IU/m L and 6 LG IU/m L 3. After entering the course of treatment, they were divided into lamivudine group (LAM group) and lamivudine group (LAM group, 23 cases). 48 patients were treated with lamivudine adefovir ester (LAM ADV group). The expression of PD-1 and PD-L1 on CD4 and CD8 T cells in peripheral blood were detected by flow cytometry at 0 ~ 12 and 24 weeks after treatment. The expression of interferon 緯 (IFN- 緯) in peripheral blood was detected by Elisa. HBV-DNA, liver function and HBV serological markers were also detected, and 26 cases of normal control group were set up. Results the expression of PD-1 PD-L1 on peripheral blood of patients with different HBV-DNA load was significantly higher than that of normal control group (P0.05), and positively correlated with HBV-DNA load (P0.05), but IFN- 緯 level was significantly lower than that of normal control group (P0.05). The expression of PD-1 pPD-L1 was significantly decreased in both groups. There was significant difference in PD-1 PD-L1 on the surface of CD4 and CD8 T cells except for CD4 PD-L1 in LAM group (P0.05). The expression of IFN- 緯 in LAM ADV group was significantly higher than that in LAM group (P0.05), and there was a significant difference between the two groups before and after 12 weeks and 24 weeks of treatment (P0.05), and the expression of IFN- 緯 in LAM ADV group was significantly higher than that in LAM group (P0.05). At 24 weeks after treatment, it rose to (24.55 鹵5.81) pg/m L, which was significantly higher than that before treatment (13.97 鹵4.13) pg/m L (P0.05), but there was no significant difference between the two groups (P0.05). Conclusion the expression of PD-1 and PD-L1 on the surface of CD4 and CD8 T cells in patients with chronic hepatitis B is positively correlated with the HBV-DNA load. Inhibiting the replication of HBV could effectively reduce the expression of PD-1nPD-L1. The rate and amplitude of PD-1pPD-L1 decrease was obviously higher than that of LAM alone, and the activity of T lymphocytes could be increased more easily.
【作者單位】： 江蘇省常州市第三人民醫(yī)院肝病研究所;
【基金】：江蘇省常州市衛(wèi)生局重大科技項(xiàng)目(編號:ZD201106)
【分類號】：R512.62

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