恩替卡韦对慢性乙型肝炎患者外周血单核细胞表面PD-1和PD-L1表达的影响  

Effect of entecavir on the expression of PD-1 and PD-L1 in peripheral mononuclear of patients withchronic hepatitis B

作　　者：张玉喜[1,2] 闫树英[1,2] 王惠成[1,2] 胡燕梅[1,2] 李阳[1,2] 

机构地区：[1]宁夏人民医院感染疾病科,宁夏银川750002 [2]西北民族大学第一附属医院,宁夏银川750002

出　　处：《宁夏医学杂志》2016年第11期991-993,共3页Ningxia Medical Journal

基　　金：宁夏科技攻关计划项目(KGX130910);宁夏科技攻关计划项目(KGX131016)

摘　　要：目的探讨恩替卡韦对慢性乙型肝炎(CHB)患者外周血单核细胞(PBMCs)表面PD-1、PD-L1的影响及其与血清HBV-DNA载量、谷丙转氨酶(ALT)之间的关系。方法收集CHB患者40例,其中2×ULN≤ALT<5×ULN 20例(A组),ALT≥5×ULN 20例(B组),健康献血者20例(C组)。A组、B组均给予恩替卡韦口服抗病毒治疗,疗程为24周。采用流式细胞术检测治疗前及治疗24周时患者PBMCs表面PD-1及其配体PDL1表达,以实时荧光定量PCR检测血清HBV-DNA,同时检测血清ALT。结果 A组、B组2组患者PBMCs表面PD-1、PD-L1表达显著高于C组(P<0.05),A组与B组比较PBMCs表面PD-1、PD-L1表达水平差异无统计学意义(P>0.05)。恩替卡韦抗病毒治疗24周时,A组、B组2组患者PBMCs表面PD-1、PD-L1表达水平均明显下降,差异有统计学意义(P<0.05),且B组较A组下降更为显著,差异有统计学意义(P<0.05);但2组患者治疗后PBMCs表面PD-1、PD-L1表达水平仍高于C组,差异有统计学意义(P<0.05)。治疗24周时A组、B组2组患者血清HBV-DNA、ALT水平均明显下降,差异有统计学意义(P<0.05),A组、B组2组患者治疗后比较,HBV-DNA及ALT水平差异无统计学意义(P>0.05)。结论恩替卡韦不但能抑制HBV-DNA合成,还可以降低CHB患者PBMCs表面PD-1、PD-L1表达水平,且在肝脏炎症损伤重的CHB患者中下降幅度更为明显。Objective Toinvestigate the effect of Entecavir on the PD - 1, PD - L1 of peripheral blood mononuclear cells （PB- MCs） in patients with chronic hepatitis B （CHB） ,and to investigate the relationship with serum HBV - DNA load,ALT. Methods 40 pa- tients with CHB were divided into two groups, the 2 × ULN ≤ ALT 〈 5 × ULN group （ group A）, ALT ≥ 5 ×ULNgroup （ group B ）, healthy blood donors （group C） and 20 cases in each group. The patients in Group A and group B were given Entecavir oral antiviral therapy,treat- ment for 24 weeks. Flow cytometry was used to detect the expression of PD - 1 and its ligand PD - L1 on the surface of PBMCs in the pa- tients before and 24 weeks of treatment ,The serum HBV- DNA was detected by real -time fluorescence quantitative PCR, and serum ala- nine aminotransferase （ALT） was detected simultaneously. Results PBMCs surface PD - 1, PD - L1 expression in groupA and groupB were significantly higher than that in group C （P 〈 0.05 ） ;PBMCs surface PD - 1, PD - L1 expression levels were not significantly different between group A and group B （P 〉0.05）. Entecavir therapy for 24 weeks,PBMCs surface PD - 1 ,PD - L1 expression levels ingroup A and group Bwere significantly decreased（P 〈0.05）. And those decreased more significantly in group B than those in group A（P 〈0.05）. PB- MCs surface PD- 1 ,PD- L1 expression level in group A and group Bwere still higher after treatment than the group C （P 〈0.05）. The serum HBV - DNA, ALT levels in ingroup A and group B were significantly decreased at 24 weeks （P 〈 0.05）. HBV - DNA and ALT lev- els in ingroup A and group B were not statistically significant after treatment （P 〉 0. 05）. Conclusion Entecavir can not only inhibit the synthesis of HBV- DNA,but also can reduce the PBMCs surface PD -1 ,PD- L1 expression levels in CHB patients,and the decrease of CHB in patients with severe liver inflanunation was more obvious.

关 键 词：慢性乙型病毒性肝炎 抗病毒治疗 程序性死亡受体1 恩替卡韦 

分 类 号：R512.62[医药卫生—内科学]