CD4~+T、CD8~+T、CD4~+/CD8~+与慢性乙肝不同中医体质存在相关性
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摘要
探讨外周血CD4~+、CD8~+T水平与慢性乙型肝炎不同中医体质的关系。选取2016年2月至2017年3月在我院治疗的慢性乙型感染患者143例,其中平和质35例、气虚质40例、阴虚质21例、湿热质20例,气郁质16例、其他11例,采用流式细胞仪检测外周血T淋巴细胞亚群。不同中医体质患者性别、年龄、病程及HBV-DNA含量比较差异无统计学意义(p>0.05);平和质患者AST为342.21(142.42,513.46)U/L,明显低于其他患者(p<0.05);气虚质患者AST为512.40(322.81,726.50)U/L,明显高于其他患者(p<0.05);气郁质及其他体质患者ALT分别为381.64(210.41,501.72)U/L和370.43(200.41,470.63)U/L,明显高于平和质、气虚质、阴虚质和湿热质患者(p<0.05);平和质和气虚质患者外周血CD4~+T细胞分别为(39.10±2.01)%和(39.10±2.01)%,明显低于阴虚质、湿热质、气郁质及其他体质患者(p<0.05);气郁质及其他体质患者CD8~+T细胞分别为(25.43±1.33)%和(25.24±1.31)%,明显低于平和质、气虚质、阴虚质和湿热质患者(p<0.05);阴虚质、气郁质及其他体质患者分别为(1.71±0.09)、(1.75±0.08)和(1.78±0.09),明显高于平和质、气虚质和湿热质患者(p<0.05)。慢性乙肝不同中医体质与CD4~+T、CD8~+T和以及肝功能有密切关系。关键词
The aim of the study was to investigate the relationship between the levels of CD4~+and CD8~+T in peripheral blood and the constitutions of traditional Chinese medicine in patients with chronic hepatitis B. 143 patients with chronic HBV infection treated in Chongqing Traditional Chinese Medicine hospital from February 2016 to March 2017 were selected. Among them, there were 35 cases of normal, 40 cases of Qi deficiency, 21 cases of Yin deficiency, 20 cases of dampness heat, 16 cases of Qi depression and 11 cases of other. Peripheral blood T lymphocyte subsets were detected by flow cytometry. The results showed that, there was no significant difference in gender, age,course of disease and HBV-DNA content between different constitutions of traditional Chinese medicine(p>0.05); AST in the patients with normal was 342.2(142.42, 513.46) U/L, significantly lower than that of other patients(p<0.05);the AST in patients with Qi deficiency was 512.40(322.81, 726.50) U/L, significantly higher than that of other patients(p<0.05); the ALT of patients with Qi depression and other constitutions was 381.64(210.41, 501.72) U/L and 370.43(200.41, 470.63) U/L, respectively, which were significantly higher than that of normal, Qi deficiency, Yin deficiency and dampness heat(p<0.05); the CD4~+T cells in peripheral blood of patients with normal and Qi deficiency was(39.10±2.01)% and(39.10±2.01)%, respectively, which was significantly lower than that of Yin deficiency, dampness heat, Qidepression and other constitutions(p<0.05); the CD8~+T cells in patients with Qi depression and other constitutions was(25.43±1.33)% and(25.24±1.31)%, successively, which was significantly lower than that of normal, Qi deficiency, Yin deficiency and dampness heat(p <0.05); the CD4~+/CD8~+of patients with Yin deficiency, Qi depression and other constitutions was(1.71±0.09),(1.75±0.08) and(1.78±0.09), successively, which was significantly higher than that of normal, Qi deficiency and dampness heat(p<0.05). Chronic hepatitis B patient in different TCM constitutions might have close relationships with CD4~+T, CD8~+T, CD4~+/CD8~+and liver function.
The aim of the study was to investigate the relationship between the levels of CD4~+and CD8~+T in peripheral blood and the constitutions of traditional Chinese medicine in patients with chronic hepatitis B. 143 patients with chronic HBV infection treated in Chongqing Traditional Chinese Medicine hospital from February 2016 to March 2017 were selected. Among them, there were 35 cases of normal, 40 cases of Qi deficiency, 21 cases of Yin deficiency, 20 cases of dampness heat, 16 cases of Qi depression and 11 cases of other. Peripheral blood T lymphocyte subsets were detected by flow cytometry. The results showed that, there was no significant difference in gender, age,course of disease and HBV-DNA content between different constitutions of traditional Chinese medicine(p>0.05); AST in the patients with normal was 342.2(142.42, 513.46) U/L, significantly lower than that of other patients(p<0.05);the AST in patients with Qi deficiency was 512.40(322.81, 726.50) U/L, significantly higher than that of other patients(p<0.05); the ALT of patients with Qi depression and other constitutions was 381.64(210.41, 501.72) U/L and 370.43(200.41, 470.63) U/L, respectively, which were significantly higher than that of normal, Qi deficiency, Yin deficiency and dampness heat(p<0.05); the CD4~+T cells in peripheral blood of patients with normal and Qi deficiency was(39.10±2.01)% and(39.10±2.01)%, respectively, which was significantly lower than that of Yin deficiency, dampness heat, Qidepression and other constitutions(p<0.05); the CD8~+T cells in patients with Qi depression and other constitutions was(25.43±1.33)% and(25.24±1.31)%, successively, which was significantly lower than that of normal, Qi deficiency, Yin deficiency and dampness heat(p <0.05); the CD4~+/CD8~+of patients with Yin deficiency, Qi depression and other constitutions was(1.71±0.09),(1.75±0.08) and(1.78±0.09), successively, which was significantly higher than that of normal, Qi deficiency and dampness heat(p<0.05). Chronic hepatitis B patient in different TCM constitutions might have close relationships with CD4~+T, CD8~+T, CD4~+/CD8~+and liver function.
引文
Bonino F.,Chiaberge E.,Maran E.,and Piantino P.,1987,Serological markers of HBV infectivity,Annali Dellistituto Superiore Di Sanità,24(2):217-223
Chi X.L.,Li S.,Xiao H.M.,Zhang C.Z.,Liu Y.Y.,Wei Z.H.,Wang J.H.,and Liu L.X.,2016,Analysis on characteristics of Chinese medicine constitution in 69 autoimmune hepatitis patients,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),57(6):492-495(池晓玲,黎胜,萧焕明,张朝臻,刘燕燕,魏泽辉,王嘉豪,刘乐鑫,2016,69例自身免疫性肝炎患者中医体质特点分析,中医杂志,57(6):492-495)
Fu X.L.,Tian Y.L.,Zang Z.D.,Zhu X.Y.,and Yin W.W.,2017,Clinical study on correlation between type 2 diabetes mellitus or impaired glucose tolerance and hepatocellular carcinoma in patients with hepatitis B cirrhosis,Aizheng Jinzhan(Oncology Progress),15(5):540-543(傅熙玲,田玉岭,臧志栋,朱晓云,殷卫卫,2017,2型糖尿病或糖耐量异常与乙型肝炎肝硬化发生肝癌的相关性研究,癌症进展,15(5):540-543)
Iannacone M.,Sitia G.,Isogawa M.,Marchese P.,Castro M.G.,Lowenstein P.R.,Chisari F.V.,Ruggeri Z.M.,and Guidotti L.G.,2005,Platelets mediate cytotoxic T lymphocyte-induced liver damage,Nature Medicine,11(11):1167
Jia H.Y.,Chen Z.,Zhou L.F.,Chen F.,Zhu H.H.,Liu J.H.,and Xu X.Y.,2005,Inhibition of binding peptides on replication of duck hepatitis B virus,Zhejiang Daxue Xuebao(Yixue ban)(Journal of Zhejiang University(Medical Sciences)),34(2):116-12(贾红宇,陈智,周林福,陈峰,朱海红,刘继洪,许晓燕,2005,结合肽抑制鸭乙型肝炎病毒复制作用的研究,浙江大学学报(医学版),34(2):116-120)
Lee W.M.,2013,Hepatitis B virus infection,N.Engl.J.Med.,337(24):353-368
Li G.M.,Zhao X.L.,Hu S.L.,Cui Z.F.,and Shi J.J.,2014,Safety and effectiveness of telbivudine in treatment of pregnant women infected with chronic hepatitis B virus,Zhonghua Yiyuan Ganranxue Zazhi(Chinese Journal of Nosocomiology),(9):2169-2171(李广明,赵小丽,胡善雷,崔中锋,史继静,2014,替比夫定治疗慢性乙型肝炎病毒感染孕妇的安全性及有效性评价,中华医院感染学杂志,(9):2169-2171)
Liu B.X.,Zhang L.L.,and Zhang W.F.,2016,Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment,Zhonghua Chuangranbin Zazhi(Chinese Journal of Infectious Diseases),34(8):480-484(刘碧霞,张伦理,张文峰,2016,慢性乙型肝炎患者抗病毒治疗与停药复发后体内乙型肝炎核心抗原特异性T淋巴细胞变化,中华传染病杂志,34(8):480-484)
Liu H.T.,Shi J.X.,Luo D.,Huang J.,Wang Q.,and Shi X.G.,2016,Literature research of medication rule of Chinese medicine treatment of chronic hepatitis B by syndrome differentiation,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),57(16):1421-1425(刘海涛,施家希,罗丹,黄娟,王奇,施旭光,2016,中医药辨证治疗慢性乙型肝炎用药规律文献研究,中医杂志,57(16):1421-1425)
Liu W.G.,2016,Innate immune defense effects of pathogenic mi croorganism infection,Kexue Tongbao(Chinese Science Bulletin),61(27):2986-2995(刘光伟,2016,病原体感染的天然免疫防御效应,科学通报,61(27):2986-2995)
Ma C.Y.,Lu Z.C.,Wang K.X.,Bie L.H.,and Sheng Q.,2016,Elevated expression of lymphocyte activation gene-3 on peripheral blood CD8+T lymphocytes in patients with chronic hepatitis B virus infection,Xibao Yu Fenzimianyixue Zazhi(Chinese Journal of Cellular and Molecular Immunology),32(4):532-537(马晨芸,陆志成,王克翔,别立翰,沈茜,2016,慢性乙型肝炎病毒感染患者外周血CD8+T淋巴细胞表面淋巴细胞活化基因3水平升高,细胞与分子免疫学杂志,32(4):532-537)
Maduna P.H.,Dolan M.,Kondlo L.,Mabuza H.,Dlamini J.N.,Polis M.,Mnisi T.,Orsega S.,Maja P.,Ledwaba L.,Molefe T.,Sangweni P.,Malan L.,Matchaba G.,Khabo P.,Grandits G.,and Neaton J.D.,2015,Morbidity and mortality according to latest CD4+cell count among HIV positive individuals in South Africa who enrolled in project Phidisa,Plos One,10(4):121843
Mio J.,Yuan C.Y.,Li Q.W.,Guo L.Y.,Jia J.W.,and Cao W.K.,2016,An analysis on correlations between expressions of CD4+and CD8+T lymphocytes in peripheral blood and quantitative level of HBs Ag in patients with chronic hepatitis Bvirus infection,Zhongguo Zhongxiyi Jiehe Jijiu Zazhi(Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care),23(4):399-403(苗静,袁晨翼,李秋伟,郭丽颖,贾建伟,曹武奎,2016,慢性乙型肝炎病毒感染患者外周血CD4+、CD8+T细胞的表达与HBs Ag定量的相关性分析,中国中西医结合急救杂志,23(4):399-403)
Pungpapong S.,Kim W.R.,and Poterucha J.J.,2007,Natural history of hepatitis B virus infection:an update for clinicians,Mayo Clinic Proceedings,82(8):967
Reng J.Z.,and Li B.,2016,Progress on whether generation and maintenance of memory T cells require chronic exposure to antigens,Kexue Tongbao(Chinese Science Bulletin),61(28):3085-3090(任甲子,李斌,2016,记忆性T细胞形成与维持是否依赖于抗原刺激的相关研究进展,科学通报,61(28):3085-3090)
Turtle C.J.,Hanafi L.A.,Berger C.,Gooley T.A.,Cherian S.,Hudecek M.,Sommermeyer D.,Melville K.,Pender B.,Budiarto T.M.,Robinson E.,Steevens N.N.,Chaney C.,Soma L.,Chen X.,Yeung C.,Wood B.,Li D.,Cao J.,Heimfeld S.,Jensen M.C.,Riddell S.R.,and Maloney D.G.,2016,CD19 CAR-T cells of defined CD4+:CD8+composition in adult B cell ALL patients,Journal of Clinical Investigation,126(6):2123
Wang L.,Xu J.,and Xia P.,2016,Bloodstream infection in a patient with liver cirrhosis caused by Vibrio vulnificus:a case report,Zhongguo Ganran Yu Hualiao Zazhi(Chinese Journal of Infection and Chemotherapy),16(2):227-228(王莉,徐静,夏萍,2016,肝硬化患者创伤弧菌血流感染1例,中国感染与化疗杂志,16(2):227-228)
Wang L.F.,Xue B.Y.,and Zhao H.B.,2015,Treating chronic infection of hepatitis B virus from kidney deficiency,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),56(17):1458-1461(万凌峰,薛博瑜,赵红兵,2015,从肾虚论治慢性乙型肝炎病毒感染,中医杂志,56(17):1458-1461)
Xiong J.H.,and Xi X.P.,2001,The relationship between changes in t-lymphocyte subsets in peripheral blood and the immune state of renal transplant recipients,Nanchang Daxue Xuebao(Yixueban)(Journal of Nanchang University(Medical Sciences)),41(3):41-43(熊建华,习小庆,2001,肾移植受者外周血T淋巴细胞亚群变化与机体免疫状态之间的关系,南昌大学学报(医学版),41(3):41-43)
Xu X.F.,Li S.,and Li H.M.,2015,K562 cells impair mitochondrial function and energy metabolism of dendritic cells in Transwell coculture system,Disanjunyidaxue Xuebao(Journal of Third Military Medical University),37(18):1854-1858(许晓风,李爽,李昊淼,2015,K562细胞对树突状细胞线粒体功能和能量代谢状态的影响,第三军医大学学报,37(18):1854-1858)
Zhuang Q.J.,LV H.,Pang Z.Q.,Chen Y.,Ma L.,Yao X.S.,Qiu and L.M.,2015,CDR3 spectratyping analysis and complementary decision area 3 sequence determination forCD4+CD25+Tregs in patients with chronic hepatitis B,Zhonghua Ganzangbin Zazhi(Chinese Journal of Hepatolo-gy),23(8):628-630(庄勤建,吕红,潘宗琴,陈宇,马龙,姚新生,邱隆敏,2015,慢性乙型肝炎患者外周血CD4+CD25+调节性T淋巴细胞受体CDR3谱系的特征分析,中华肝脏病杂志,23(8):628-630)
Chi X.L.,Li S.,Xiao H.M.,Zhang C.Z.,Liu Y.Y.,Wei Z.H.,Wang J.H.,and Liu L.X.,2016,Analysis on characteristics of Chinese medicine constitution in 69 autoimmune hepatitis patients,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),57(6):492-495(池晓玲,黎胜,萧焕明,张朝臻,刘燕燕,魏泽辉,王嘉豪,刘乐鑫,2016,69例自身免疫性肝炎患者中医体质特点分析,中医杂志,57(6):492-495)
Fu X.L.,Tian Y.L.,Zang Z.D.,Zhu X.Y.,and Yin W.W.,2017,Clinical study on correlation between type 2 diabetes mellitus or impaired glucose tolerance and hepatocellular carcinoma in patients with hepatitis B cirrhosis,Aizheng Jinzhan(Oncology Progress),15(5):540-543(傅熙玲,田玉岭,臧志栋,朱晓云,殷卫卫,2017,2型糖尿病或糖耐量异常与乙型肝炎肝硬化发生肝癌的相关性研究,癌症进展,15(5):540-543)
Iannacone M.,Sitia G.,Isogawa M.,Marchese P.,Castro M.G.,Lowenstein P.R.,Chisari F.V.,Ruggeri Z.M.,and Guidotti L.G.,2005,Platelets mediate cytotoxic T lymphocyte-induced liver damage,Nature Medicine,11(11):1167
Jia H.Y.,Chen Z.,Zhou L.F.,Chen F.,Zhu H.H.,Liu J.H.,and Xu X.Y.,2005,Inhibition of binding peptides on replication of duck hepatitis B virus,Zhejiang Daxue Xuebao(Yixue ban)(Journal of Zhejiang University(Medical Sciences)),34(2):116-12(贾红宇,陈智,周林福,陈峰,朱海红,刘继洪,许晓燕,2005,结合肽抑制鸭乙型肝炎病毒复制作用的研究,浙江大学学报(医学版),34(2):116-120)
Lee W.M.,2013,Hepatitis B virus infection,N.Engl.J.Med.,337(24):353-368
Li G.M.,Zhao X.L.,Hu S.L.,Cui Z.F.,and Shi J.J.,2014,Safety and effectiveness of telbivudine in treatment of pregnant women infected with chronic hepatitis B virus,Zhonghua Yiyuan Ganranxue Zazhi(Chinese Journal of Nosocomiology),(9):2169-2171(李广明,赵小丽,胡善雷,崔中锋,史继静,2014,替比夫定治疗慢性乙型肝炎病毒感染孕妇的安全性及有效性评价,中华医院感染学杂志,(9):2169-2171)
Liu B.X.,Zhang L.L.,and Zhang W.F.,2016,Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment,Zhonghua Chuangranbin Zazhi(Chinese Journal of Infectious Diseases),34(8):480-484(刘碧霞,张伦理,张文峰,2016,慢性乙型肝炎患者抗病毒治疗与停药复发后体内乙型肝炎核心抗原特异性T淋巴细胞变化,中华传染病杂志,34(8):480-484)
Liu H.T.,Shi J.X.,Luo D.,Huang J.,Wang Q.,and Shi X.G.,2016,Literature research of medication rule of Chinese medicine treatment of chronic hepatitis B by syndrome differentiation,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),57(16):1421-1425(刘海涛,施家希,罗丹,黄娟,王奇,施旭光,2016,中医药辨证治疗慢性乙型肝炎用药规律文献研究,中医杂志,57(16):1421-1425)
Liu W.G.,2016,Innate immune defense effects of pathogenic mi croorganism infection,Kexue Tongbao(Chinese Science Bulletin),61(27):2986-2995(刘光伟,2016,病原体感染的天然免疫防御效应,科学通报,61(27):2986-2995)
Ma C.Y.,Lu Z.C.,Wang K.X.,Bie L.H.,and Sheng Q.,2016,Elevated expression of lymphocyte activation gene-3 on peripheral blood CD8+T lymphocytes in patients with chronic hepatitis B virus infection,Xibao Yu Fenzimianyixue Zazhi(Chinese Journal of Cellular and Molecular Immunology),32(4):532-537(马晨芸,陆志成,王克翔,别立翰,沈茜,2016,慢性乙型肝炎病毒感染患者外周血CD8+T淋巴细胞表面淋巴细胞活化基因3水平升高,细胞与分子免疫学杂志,32(4):532-537)
Maduna P.H.,Dolan M.,Kondlo L.,Mabuza H.,Dlamini J.N.,Polis M.,Mnisi T.,Orsega S.,Maja P.,Ledwaba L.,Molefe T.,Sangweni P.,Malan L.,Matchaba G.,Khabo P.,Grandits G.,and Neaton J.D.,2015,Morbidity and mortality according to latest CD4+cell count among HIV positive individuals in South Africa who enrolled in project Phidisa,Plos One,10(4):121843
Mio J.,Yuan C.Y.,Li Q.W.,Guo L.Y.,Jia J.W.,and Cao W.K.,2016,An analysis on correlations between expressions of CD4+and CD8+T lymphocytes in peripheral blood and quantitative level of HBs Ag in patients with chronic hepatitis Bvirus infection,Zhongguo Zhongxiyi Jiehe Jijiu Zazhi(Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care),23(4):399-403(苗静,袁晨翼,李秋伟,郭丽颖,贾建伟,曹武奎,2016,慢性乙型肝炎病毒感染患者外周血CD4+、CD8+T细胞的表达与HBs Ag定量的相关性分析,中国中西医结合急救杂志,23(4):399-403)
Pungpapong S.,Kim W.R.,and Poterucha J.J.,2007,Natural history of hepatitis B virus infection:an update for clinicians,Mayo Clinic Proceedings,82(8):967
Reng J.Z.,and Li B.,2016,Progress on whether generation and maintenance of memory T cells require chronic exposure to antigens,Kexue Tongbao(Chinese Science Bulletin),61(28):3085-3090(任甲子,李斌,2016,记忆性T细胞形成与维持是否依赖于抗原刺激的相关研究进展,科学通报,61(28):3085-3090)
Turtle C.J.,Hanafi L.A.,Berger C.,Gooley T.A.,Cherian S.,Hudecek M.,Sommermeyer D.,Melville K.,Pender B.,Budiarto T.M.,Robinson E.,Steevens N.N.,Chaney C.,Soma L.,Chen X.,Yeung C.,Wood B.,Li D.,Cao J.,Heimfeld S.,Jensen M.C.,Riddell S.R.,and Maloney D.G.,2016,CD19 CAR-T cells of defined CD4+:CD8+composition in adult B cell ALL patients,Journal of Clinical Investigation,126(6):2123
Wang L.,Xu J.,and Xia P.,2016,Bloodstream infection in a patient with liver cirrhosis caused by Vibrio vulnificus:a case report,Zhongguo Ganran Yu Hualiao Zazhi(Chinese Journal of Infection and Chemotherapy),16(2):227-228(王莉,徐静,夏萍,2016,肝硬化患者创伤弧菌血流感染1例,中国感染与化疗杂志,16(2):227-228)
Wang L.F.,Xue B.Y.,and Zhao H.B.,2015,Treating chronic infection of hepatitis B virus from kidney deficiency,Zhongyi Zazhi(Journal of Traditional Chinese Medicine),56(17):1458-1461(万凌峰,薛博瑜,赵红兵,2015,从肾虚论治慢性乙型肝炎病毒感染,中医杂志,56(17):1458-1461)
Xiong J.H.,and Xi X.P.,2001,The relationship between changes in t-lymphocyte subsets in peripheral blood and the immune state of renal transplant recipients,Nanchang Daxue Xuebao(Yixueban)(Journal of Nanchang University(Medical Sciences)),41(3):41-43(熊建华,习小庆,2001,肾移植受者外周血T淋巴细胞亚群变化与机体免疫状态之间的关系,南昌大学学报(医学版),41(3):41-43)
Xu X.F.,Li S.,and Li H.M.,2015,K562 cells impair mitochondrial function and energy metabolism of dendritic cells in Transwell coculture system,Disanjunyidaxue Xuebao(Journal of Third Military Medical University),37(18):1854-1858(许晓风,李爽,李昊淼,2015,K562细胞对树突状细胞线粒体功能和能量代谢状态的影响,第三军医大学学报,37(18):1854-1858)
Zhuang Q.J.,LV H.,Pang Z.Q.,Chen Y.,Ma L.,Yao X.S.,Qiu and L.M.,2015,CDR3 spectratyping analysis and complementary decision area 3 sequence determination forCD4+CD25+Tregs in patients with chronic hepatitis B,Zhonghua Ganzangbin Zazhi(Chinese Journal of Hepatolo-gy),23(8):628-630(庄勤建,吕红,潘宗琴,陈宇,马龙,姚新生,邱隆敏,2015,慢性乙型肝炎患者外周血CD4+CD25+调节性T淋巴细胞受体CDR3谱系的特征分析,中华肝脏病杂志,23(8):628-630)