恩替卡韦联合苦参素改善HBeAg阳性慢性乙型肝炎患者Th1/Th2失平衡临床研究  

Clinical study of entecavir combined with kushenin improving the Th1/Th2 imbalance in patients with HBeAg-positive chronic hepatitis B

作　　者：张毅[1] 余永胜[1] 汤正好[1] 陈小华[1] 王鹏[1] 江红[1] 奚敏[1] 臧国庆[1] ZHANG Yi YU Yongsheng TANG Zhenghao CHEN Xiaohua WANG Peng JIANG Hong XI Min ZANG Guoqing(Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People＇s Hospital, Shanghai 200233, Chin)

机构地区：[1]上海交通大学附属第六人民医院感染病科,上海200233

出　　处：《中国临床药理学与治疗学》2016年第10期1168-1172,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：上海市卫生和计划生育委员会中医药科研基金(2014JQ019A)

摘　　要：目的:探讨恩替卡韦联合苦参素对HBe Ag阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者Th1/Th2失平衡的影响。方法:将216例HBe Ag阳性CHB患者随机分为治疗组和对照组。治疗组112例给予恩替卡韦联合苦参素治疗,对照组104例给予恩替卡韦治疗,疗程48周。治疗48周后,应用ELISA检测患者外周血Th1型细胞因子(IFN-γ、IL-2)和Th2型细胞因子(IL-4、IL-10)的表达水平,应用实时定量PCR检测患者外周血Th1细胞特征性转录因子(T-bet)和Th2细胞特征性转录因子(GATA3)mRNA的表达水平。结果:治疗48周后,治疗组IFN-γ、IL-2的表达水平较对照组明显升高[(68.32±9.67)pg/m L vs(35.24±7.49)pg/m L,(216.81±31.55)pg/m L vs(115.63±29.13)pg/m L;t1=27.96,t2=24.43;P1、P2均<0.01];而治疗组IL-4、IL-10的表达水平较对照组明显降低[(18.79±5.83)pg/m L vs(22.58±5.32)pg/m L,(133.75±29.21)pg/m L vs(143.17±32.96)pg/m L;t3=4.98,t4=2.23;P3<0.01,P4<0.05]。治疗组IFN-γ与IL-4比值IFN-γ/IL-4较对照组明显增大(3.59±0.76 vs 1.61±0.53,t=22.05,P<0.01)。治疗48周后,治疗组T-bet mRNA的表达水平较对照组明显升高(1.52±0.41 vs 0.83±0.29,t=14.18,P<0.01);而治疗组GATA3 mRNA的表达水平较对照组明显降低(0.96±0.24 vs 1.05±0.37,t=2.14,P<0.05)。治疗组T-bet mRNA与GATA3 mRNA比值T-bet/GATA3较对照组明显增大(1.60±0.39 vs 0.81±0.32,t=16.20,P<0.01)。结论:恩替卡韦联合苦参素可以促进HBe Ag阳性CHB患者Th1型细胞因子的分泌,抑制Th2型细胞因子的分泌,促使HBe Ag阳性CHB患者外周血Th细胞向Th1细胞分化,使其Th1/Th2失平衡得到改善。AIM： To evaluate the effects of entecavir（ ETV） combined with kushenin on the Th1 /Th2 imbalance in patients with HBe Ag-positive chronic hepatitis B（ CHB）. METHODS： 216 patients with HBe Ag-positive CHB were randomly divided into treatment group（ n = 112） and control group（ n= 104）. Patients in the control group were treated with ETV, while patients in the treatment group were treated with ETV combined with kushenin. All patients were treated for 48 weeks. At 48 weeks of treatment, the expressions of Th1-type cytokines（ IFN-γ,IL-2） and Th2-type cytokines（ IL-4,IL-10） were measured by ELISA and the expression of T-bet and GATA3 mRNA was assayed by quantitative real-time PCR. RESULTS： At 48 weeks of treatment,compared with the control group,（ 1）the levels of IFN-γ and IL-2 in the treatment group significantly increased [（ 68. 32 ± 9. 67） pg / m L vs（ 35. 24 ± 7. 49） pg /m L,（ 216. 81 ± 31. 55） pg /m L vs（ 115. 63 ± 29. 13） pg / m L; t1= 27. 96,t2=24. 43; both P1,P2〈 0. 01];（ 2） the levels of IL-4 and IL-10 in the treatment group significantly decreased [（ 18. 79 ± 5. 83） pg / m L vs（ 22. 58 ±5. 32） pg / m L,（ 133. 75 ± 29. 21） pg / m L vs（ 143. 17 ± 32. 96） pg /m L; t3= 4. 98,t4= 2. 23;P3〈 0. 01,P4〈 0. 05];（ 3） the ratio of IFN-γ / IL-4 in the treatment group significantly increased（ 3. 59 ± 0. 76 vs 1. 61 ± 0. 53,t = 22. 05,P 〈0. 01）;（ 4） the expression of T-bet mRNA in the treatment group significantly increased（ 1. 52 ± 0. 41 vs 0. 83 ± 0. 29,t = 14. 18,P 〈 0. 01）;（ 5） the expression of GATA3 mRNA in the treatment group significantly decreased（ 0. 96 ± 0. 24 vs 1. 05 ±0. 37,t = 2. 14,P 〈 0. 05）;（ 6） the ratio of T-bet /GATA3 in the treatment group significantly increased（ 1. 60 ± 0. 39 vs 0. 81 ± 0. 32,t = 16. 20,P 〈0. 01）. CONCLUSION： The treatment of ETV combined with kushenin can promote the secretion of Th1-type cytokines and inhibit the secretion of Th2-type cytokines in

关 键 词：慢性乙型肝炎 恩替卡韦 苦参素 TH1细胞 TH2细胞 细胞因子 

分 类 号：R575.1[医药卫生—消化系统]