苦参素对慢性乙型肝炎患者外周血CTL表面PD-1表达的影响

Effect of kurarinol on peripheral blood CTL surface PD-1 expression of patients with chronichepatitis B

目的通过研究苦参素对慢性乙型肝炎（CHB）患者细胞毒性T淋巴细胞（CTL）表面程序性死亡受体-1（PD-1）表达的影响，探讨苦参素抗病毒的机制。方法69例CHB患者，HBVDNA≥104拷贝／ml，HBeAg阳性，人白细胞抗原（HLA）-A2阳性，丙氨酸转氨酶（ALT）〉2×正常值上限（ULN），69例随机分为二组：治疗组34例，用苦参素葡萄糖注射液600mg，静脉滴注，每131次，1个月后改为苦参素胶囊200mg口服，每日3次，水飞蓟宾葡甲胺片200mg口服，每日3次，对照组35例，只用水飞蓟宾葡甲胺片，用法用量同治疗组。分析比较3个月后患者的外周血HBV特异性CTL表面PD一1表达、非特异性CTL表面PD-1表达和HBV特异性CTL水平，HBVDNA和HBeAg阴转率及肝功能。结果治疗3个月后，治疗组外周血HBV特异性CTL表面PD．1表达较治疗前下降（t=2．39，P〈0．05），也较对照组治疗后3个月下降（t=2．26，P〈0．05），HBV特异性CTL水平较治疗前升高（t=3．01，P〈0．01），也较对照组治疗后升高（t=2．65，P〈0．05）。非特异性CTL表面PD．1表达与治疗前比较，差别无统计学意义（P〉0．05），与对照组治疗后比较，差别无统计学意义（P〉0．05）。HBVDNA阴转（HBVDNA〈500拷贝／m1）11例（32．35％），高于对照组治疗后（2例，占5．71％），=7．99，P〈0．01，HBeAg阴转9例（26．47％），高于对照组治疗后（1例，占2．86％），X2=7．75，P〈0．01。结论苦参素通过下调CHB患者外周血HBV特异性CTL表面PD-1表达，提高HBV特异性CTL水平，是苦参素清除或抑制CHB患者HBV的可能机制之一。

Objective To explore the anti-viral mechanism of kurarinol through studying its influence on eytotoxic T lymphocyte （CTL） surface program death receptor-1 （ PD-1 ） expression of patients with chronic hepatitis B （CHB）. Methods 69 cases of CHB, HBV DNA ≥ 104 copies/ml, HBeAg positive, human leukocyte antigen（HLA） -A2 positive, alanine aminotransferase （ALT） 〉 2 × upper limit of normal value （ULN）. 69 cases were randomly divided into two groups：34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping, once a day, one month later, 200 mg of kurarinol capsule was used orally,three times a day and,200 mg of silybin meglumine tablet was used orally, three times a day. 35 cases in control group,only silibin meglumine tablet was used, method and dosage were the same as those of treatment group. Three months later, their peripheral blood HBV specific CTL surface PD-1 expression, non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared. Results 3 months after treatment, peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment（t = 2.39 ,P 〈 0.05） ,it also decreased compared with that of the control group 3 months after treatment（t =2.26 ,P 〈 0. 05 ）, HBV specific CTL increased compared with that before treatment（ t = 3.01 ,P 〈 0. 01 ）,it also increased compared with that of the control group after treatment （t = 2.65, P 〈0.05）. There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment（P 〉 0. 05） ,and there was no significant difference compared with that of the control group after treatment（P 〉 0. 05 ）. HBV DNA ofll cases （ 32.5% ） turned negative（ HBV DNA 〈 500 copies/ ml） , higher than that of the control group after treatment （ 2 cases,5.71% ）X2 = 7.99, P 〈 0. 01, HBeAg of 9 cases（26.47% ） turned negative, higher than that of the control group after treatment（ 1 case,2. 86% ） ,X2 = 7.75,P 〈 0.01. Conclusion Kurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients, which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.