柴胡解毒汤联合阿德福韦酯治疗慢性乙型肝炎患者外周血淋巴细胞亚群和细胞因子的变化

doi:10.3969/j.issn.1672-5069.2017.01.010

摘要/Abstract

摘要： 目的分析柴胡解毒汤联合阿德福韦酯片治疗慢性乙型肝炎（CHB）患者体内病毒水平与外周血淋巴细胞亚群和细胞因子的变化的关系,为临床治疗CHB患者提供新的思路。方法 2013年12月至2015年3月间我院收治的CHB患者60例,被分为A组、B组和C组。给予A组服用柴胡解毒汤治疗,给予B组服用阿德福韦酯片,C组在B组基础上,服用柴胡解毒汤治疗。3组均观察12 m。采用ELISA法检测血清HBV标记物和血清IL-2水平,采用荧光定量PCR法检测血清HBV DNA水平,使用贝克曼库尔特流式细胞仪检测T细胞亚群和自然杀伤细胞百分比。结果在治疗12 m末,C组患者HBV DNA阴转率、ALT复常率和HBeAg阴转率分别为85.00%、80.00%和80.00%,均显著高于A组（分别为50.00%、65.00%和45.00%）或B组（分别为65.00%、55.00%和50.00%,P<0.05）;C组患者外周血CD3⁺T细胞、CD4⁺T细胞和CD4⁺/CD8⁺细胞比值分别为（65.2±9.6）%、（28.4±7.2）%和（1.1±0.3）,与A组【分别为（57.5±8.7）%、（45.7±5.4）%和（1.8±0.6）】或B组【（55.7±6.3）%、（23.2±9.5）%和（0.9±0.1）】比,差异显著（P<0.05）;C组患者外周血CD8⁺T细胞为（25.3±4.1）%,显著低于B组[（28.7±4.3)%, P<0.05];C组患者外周血NK细胞与A组或B组比,无显著性差异（P>0.05）,但血清IL-2水平【（3.6±0.8） ng/mL】显著高于B组【（2.8±0.5） ng/mL,P<0.05】;A组CD4⁺T细胞增加与HBV DNA载量减少呈显著正相关（P<0.05）;C组CD3⁺T细胞增加、CD8⁺T细胞减少、NK细胞增加与HBV DNA载量减少呈正相关（P<0.05）。结论柴胡解毒汤联合阿德福韦酯片治疗慢性乙型肝炎患者可调节外周血淋巴细胞比例失调,打破免疫耐受,恢复肝功能,提高抗病毒效果。

关键词: 慢性乙型肝炎, 柴胡解毒汤, 阿德福韦酯, 淋巴细胞亚群

Abstract: Objectives To investigate the changes of peripheral blood T lymphocyte subsets and IL-2 in patients with chronic hepatitis B（CHB） receiving Bupleurum Jiedu decoction combined with adefovir dipivoxil （ADV） therapy. Methods 60 patients with CHB were recruited in our hospital between December 2013 and March 2015. They were treated with Bupleurum Jiedu decoction in group A （n=20）,with ADV in group B （n=20） and with both in group C（n=20）. All regimens lasted for 12 months. Serum HBV markers and IL-2 were detected by ELISA,and T lymphocyte subsets and natural killer cells were detected by flow cytometry. Results At the end of 12-month treatment,the serum HBV DNA loss,ALT normalization rate and HBeAg negative rate in group C were 85.00%,80.00% and 80.00%,much higher than in group A（50.00%,65.00% and 45.00%,respectively） or in group B（65.00%,55.00% and 50.00%,respectively,P<0.05）;the proportion of peripheral CD3⁺T cells and CD4⁺T cells and ratio of CD4⁺/CD8⁺ cells in groups C were（65.2±9.6）%,（28.4±7.2）% and（1.1±0.3）,significantly different as compared to those in group A 【（57.5±8.7）%,（45.7±5.4）% and（1.8±0.6）, respectively or group B（55.7±6.3）%,（23.2±9.5）% and（0.9±0.1）,respectively,P<0.05];the proportion of CD8⁺T cells in group C was （25.3±4.1）%,much lower than in group B [（28.7±4.3） %,P<0.05];the proportion of NK cells in group C was not significantly different as compared to that in group A or in group B（P>0.05）,while serum IL-2 level【（3.6±0.8）ng/mL】 was much higher than in group B【（2.8±0.5）ng/mL,P<0.05】;the increased CD4⁺T cells was positively correlated to serum HBV DNA loss in group A（P<0.05） and the increased CD3⁺T cells, decreased CD8⁺T cells and increased NK cells were positively correlated to serum HBV DNA loss in group C（P<0.05）. Conclusions The application of Bupleurum Jiedu decoction combined with adefovir dipivoxil can adjust lymphocyte dysfunction,break immune tolerance and improve the recovery of liver functions.

Key words: Hepatitis B, Herbal medicine, Adefovir dipivoxil, Peripheral lymphocyte subsets

肖玉柱. 柴胡解毒汤联合阿德福韦酯治疗慢性乙型肝炎患者外周血淋巴细胞亚群和细胞因子的变化[J]. 实用肝脏病杂志, 2017, 20(1): 34-37.

Xiao Yuzhu.. Changes of peripheral blood T lymphocyte subsets and IL-2 in patients with chronic hepatitis B receiving Bupleurum Jiedu decoction combined with adefovir dipivoxil therapy[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(1): 34-37.

参考文献

[1] Liu XR,Li R,Yu Xl,et al. Hepatitis B virus can be inhibited by DNA methyltransferase 3a via specific zinc-finger-induced methylation of the X promoter. Biochemistry,2014,79（2）:111-123.
[2] Lyu JJ,Yu S,Wang YF,et al. Anti-hepatitis B virus norbisabolane sesquiterpenoids from phyllanthus acidus and the establishment of their absolute configurations using theoretical calculations. J Organ Chem,2014,79（12）:5432-5447.
[3] 黄英男,吴昊. 乙型肝炎肝硬化抗病毒治疗研究进展. 复旦学报（医学版）,2013,40（2）:233-238.
[4] 李庆,武永乐,李冰,等. 慢性乙型肝炎患者外周血调节性B细胞与乙型肝炎病毒DNA定量的相关性.北京医学,2014,36（12）:1056-1057.
[5] He N,Wang F,Ma C,et al. Chemiluminescence analysis for HBV-DNA hybridization detection with magnetic nanoparticles based DNA extraction from positive whole blood samples. J Biomed Nanaotechnol,2013,9（2）:267-273.
[6] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2015年版）. 实用肝脏病杂志,2016,19（3）：Ⅴ-ⅩⅩⅢ.
[7] Li MR,Xi HL,Wang QH,et al. Kinetics of serum HBsAg in Chinese patients with chronic HBV infection with long-term adefovir dipivoxil treatment. Chin J Med,2014,127（11）:2101-2104.
[8] 胥萍,陈慧,吴敏娟,等. 乙型肝炎患者外周血HBV抗原抗体表达及病毒载量与T细胞亚群检测分析.现代检验医学杂志,2013,28（3）:44-47.
[9] 史贵秀,赵新平,褚建伟,等. 替比夫定对慢性HBV感染孕妇CD4 + CD25 + 调节性T细胞的影响.国际医药卫生导报,2014,20（18）:2811-2815.
[10] 矫淑媛,张学平. HBsAg定量与HBV-DNA联合检测在慢性乙型肝炎中的临床意义.标记免疫分析与临床,2015,22（12）:1245-1247,1213.
[11] Xu L,Yin W,Sun R,et al. Liver type i regulatory T cells suppress germinal center formation in HBV-tolerant mice. Proc Natl Acad Sci USA,2013,110（42）:16993-16998.
[12] 吴杭源,尤德宏.替比夫定对e抗原阳性慢性乙型肝炎患者外周血NK细胞水平的影响. 现代中西医结合杂志,2013,22（6）:621-622.
[13] 卢林,曾令伟. 调节性T淋巴细胞在乙型肝炎慢性化过程中的作用. 重庆医学,2013,42（4）:459-461.
[14] 李松,崔丽安,施伯安,等. 柴胡解毒汤治疗慢性乙型肝炎肝纤维化的临床研究. 陕西中医,2015,36（9）:1136-1137.
[15] 侯珊珊,赵远红. 循经辨治腮腺混合瘤的经验.江苏中医药,2015,47（10）:25-26.
[16] Xu Y,Wu XN,Shi YW,et al. Baseline hepatitis B virus DNA level is a promising factor for predicting the 3rd month virological response to entecavir therapy:A study of strict defined hepatitis B virus Induced cirrhosis. Chin J Med,2015,128（14）:1867-1872.
[17] 祖述臣. 大柴胡汤加减联合西医疗法治疗脑卒中. 吉林中医药,2015,35（11）:1115-1117.
[18] 李娜,马翠翠,李楠,等. “清热解毒、消肿排脓”法联合刺络、中药足浴治疗急性化脓性扁桃体炎疗效观察. 现代中西医结合杂志,2015,24（14）:1510-1512.
[19] Song GJ,Rao HY,Feng B,et al. Association between CISH polymorphisms and spontaneous clearance of hepatitis B virus in hepatitis B extracellular antigen-positive patients during immune active phase. Chin J Med,2014,127（9）:1691-1695.
[20] 赵蕊,赵跃,曲美晶,等. 疏肝解毒汤治疗慢性乙型病毒性肝炎疗效观察. 陕西中医,2014,35（2）:170-171.