目的 研究聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者外周血T淋巴细胞亚群和血清细胞因子水平的变化.方法 2014年1月~2016年1月我院收治的184例慢性乙型肝炎患者,92例接受聚乙二醇干扰素α-2b联合恩替卡韦治疗48 w,另92例只接受恩替卡韦治疗.使用流式细胞仪检测外周血T淋巴细胞亚群,采用放射免疫法检测血清IL-6、INF-ɑ、IL-4,采用酶联免疫吸附法检测血清IL-17、TGF-β1和HBV标记物,采用荧光定量PCR法检测血清HBV DNA、核转录因子RORγt、Foxp3、IL-17mRNA.结果 在停药随访24 w,联合组与恩替卡韦组血清HBV DNA阴转率分别为86.96%和84.78%(P>0.05);联合组血清HBeAg阴转率为28.89%(13/45),与恩替卡韦组的15.22%(7/46)比,无显著性差异(P>0.05);联合组血清ALT水平为(34.6±11.6)U/L,显著低于恩替卡韦组[(64.6±20.5)U/L,P<0.05];联合组外周血CD3+、CD4+细胞和CD4+/CD8+比值分别为(75.6±14.5)%、(42.7±10.3)%和(1.4±0.6),显著高于恩替卡韦组[(66.8±14.4)%、(36.7±8.5)%和(1.0±0.5),P<0.05],CD8+细胞百分比为(29.3±7.3)%,显著低于恩替卡韦组[(34.8±8.5)%,P<0.05],两组NK细胞百分比比较无显著性差异(P>0.05);治疗前两组血清IL-6、IL-17、IL-4、INF-ɑ、TGF-β1水平比较无显著性差异(P>0.05),治疗后联合组血清IL-6水平为(6.8±1.2)pg/ml,显著高于恩替卡韦组[(3.5±0.8)pg/ml,P<0.05],IL-17水平为(0.7±0.3)pg/ml,显著低于恩替卡韦组[(2.8±0.9)pg/ml,P<0.05],IL-4水平为(1.4±0.5)pg/ml,显著低于恩替卡韦组[(3.8±1.5) pg/ml,P<0.05],INF-ɑ 水平为(4.0±1.3)pg/ml,显著高于恩替卡韦组[(2.6 ±0.9)pg/ml,P<0.05],两组血清TGF-β1水平比较无显著性差异(P>0.05);治疗前两组血清Foxp3、IL-17和RORγt mRNA水平比较无显著性差异(P>0.05),治疗后联合组血清RORγt水平为(0.86±0.31),显著低于恩替卡韦组[(1.56±0.43),P>0.05],而两组血清Foxp3和IL-17mRNA水平比较无显著性差异(P>0.05).结论 聚乙二醇干扰素α-2b能通过调控细胞因子和核转录因子水平,从多个环节调控慢性乙型肝炎患者免疫功能,发挥抗病毒作用.%Objective To investigate the effect of pegylated interferon α-2b on peripheral blood T lymphocyte subsets and serum cytokine levels in patients with chronic hepatitis B. Methods 184 patients with chronic hepatitis B were recruited in our hospital between January 2014 and January 2016,and 92 patients were treated with combination of pegylated interferon α-2b and entecavir for 48 weeks,and 92 cases were with entecavir alone. The liver function indexes,serum cytokines IL-6,INF-α,IL-17,IL-4 and TGF-β1,peripheral blood T lymphocyte subsets and nuclear transcription factor(Foxp3,RORγt,IL-17)mRNA were evaluated in all patients before and after treatment. Results At the end of 24 w follow-up after discontinuation of the regimen, serum HBV DNA negative rate in the combined group and entecavir group were 86.96% and 84.78%,respectively (P>0.05),and serum HBeAg negative rate in combined group was 28.89%(13/45),without significant difference as compared with that in entecavir group [15.22%(7/46),P>0.05];there were no significant differences before treatment between the two groups(P>0.05)as respect to serum TBIL,ALT,ALB levels and PTA,while serum ALT level in the combination group at the time of follow-up was(34.6±11.6)U/L,significantly lower than (64.6 ±20.5)U/L(P<0.05)in the entecavir group;before treatment,the percentage of CD3+,CD8+,CD4+cells and the ratio of CD4+/CD8+had no significant difference between the two groups(P>0.05),while after treatment,the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+in peripheral blood in combination group were(75.6±14.5)%,(42.7±10.3)% and(1.4±0.6),significantly higher than those in the entecavir group [(66.8±14.4)%,(436.7±8.5)% and(1.0±0.5),P<0.05];the percentage of CD8+cells was(29.3±7.3)%,significantly lower than that in the entecavir Group [(34.8±8.5)%,P<0.05];there was no significant difference between the two groups(P>0.05)as respect to the percentage of NK cells;before treatment,serum levels of IL-6,IL-17,IL-4,INF-α and TGF-β1 showed no significant differences between the two groups(P>0.05),while after the treatment,serum level of IL-6 in the combination group was(6.8 ±1.2)pg/ml, significantly higher than that in the entecavir group[(3.5±0.8)pg/ml,P<0.05];serum IL-17 level was(0.7±0.3)pg/ml,significantly lower than that in the entecavir group [(2.8±0.9)pg/ml,P<0.05];serum IL-4 level was(1.4±0.5)pg/ml,significantly lower than that in the entecavir group [(3.8 ±1.5)pg/ml,P<0.05];serum level of INF-α in the combination group was(4.0±1.3)pg/ml,significantly higher than that in the entecavir group [(2.6±0.9)pg/ml,P<0.05];there was no significant difference between the two groups(P>0.05)as respect to serum level of TGF-β1;serum levels of RORγt,Foxp3 and IL-17mRNA before treatment were not significantly different between the two groups(P>0.05),while serum level of RORγt in the combination group after treatment was(0.86±0.31),significantly lower than that in the entecavir group [(1.56±0.43),P<0.05],and there were no significant differences between the two groups(P>0.05)as respect to serum Foxp3 and IL-17 mRNA levels. Conclusion Pegylated interferon α-2b can effectively improve the immune functions of patients with chronic hepatitis B by regulating transcription and expression of cytokines from various aspects,which has good clinical implication for patients with chronic hepatitis B.
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