肺痨康对实验性结核小鼠免疫调节作用的研究
|
摘要
目的：通过肺痨康(FLK)对实验性结核小鼠免疫指标的观察,研究肺痨康的免疫调节抗结核作用,为肺痨康治疗肺结核提供实验依据。
方法动物造模后,随机分为FLK高剂量组、FLK中剂量组、FLK小剂量组、利福平组、异烟肼组、肺痨康异烟肼组、肺痨康利福平组,另设空白对照组,分别给予肺痨康、利福平、生理盐水灌胃28天,观察实验小鼠胸腺指数、T淋巴细胞亚群、IFN-γ、IgG改变情况及小鼠肝肺的病理学检测。
结果：①FLK高剂量组能明显增加小鼠胸腺指数(P<0.05)；②FLK高剂量组CD4+T细胞数显著升高(P<0.01,P<0.05)；CD8+各组之间比较差异无显著性(P>0.05)；模型组CD4+/CD8+比值显著降低,其差异有显著性(P<0.01),FLK高剂量组明显减轻CD4+/CD8‘比值下降,其差异有显著性(P<0.01)；③FLK高剂量组增加小鼠结核模型血浆IFN-γ和IgG水平(P<0.05)。④与抗痨西药组比较,经病理学组织学观察,肺痨康加抗痨药组肝脏多发性坏死病变明显减轻。结论：①肺痨康治疗结核病具有免疫调节抗结核的作用。②肺痨康和西药组合用对结核小鼠模型的治疗有协同增效的作用；③肺痨康对抗痨化学疗法所致肝损害有一定的保护作用。
Objective To study the effect of FeiLao-kang (FLK) on the changes of immunological indices of mouse tuberculosis model and provide the research evidence of FLK for the treatment of tuberculosis.
Methods After the animal model establishment, the mice were randomly divided into the following groups:high-dose group of FLK, moderate-dose group of FLK, group of RFP, group of INH, group of FLK add RFP, group of FLK add INH and a control group. The RFP capsules, FLK, NS were given separately for 28 days. To observe the changes of thymus index, T-lymphocyte subsets, IFN-y, IgG in experiment mouse.
Result①The high-dose group of FLK to a marked increase in thymus index of mice (P<0.05);②The number of CD4+ T cells increased significantly in high dose group of FLK (P<0.01, P<0.05); the number of CD8+ in each group Comparison between the difference was not significant (P> 0.05); The ratio of CD4+ /CD8+ were significantly in lower model group, the difference was significant (P<0.01), The ratio of CD4+ /CD8+ significantly reduce the decreased in high-dose group of FLK,the difference was significant (P<0.01);③the serum levels of IFN-y and IgG under the groups treated with high-dose FLK was increased (P<0.05).④To compare with the latter line antituberculosis drug group:to observe by the result of pathological histology, liver multiple thanatosis had lessened in FeiLao-kang group and the latter line antituberculosis drug group.
Conclusion①FLK show definite immuno regulatory and anti-tuberculosis effects.②In the animal experiment, we can get good therapeutic efficacy from using FeiLao-kang group to treat TB.③FeiLao-kang had the certain protecting effect on liver pathologic lesion induced by antiphtisy and chemotherapy.
方法动物造模后,随机分为FLK高剂量组、FLK中剂量组、FLK小剂量组、利福平组、异烟肼组、肺痨康异烟肼组、肺痨康利福平组,另设空白对照组,分别给予肺痨康、利福平、生理盐水灌胃28天,观察实验小鼠胸腺指数、T淋巴细胞亚群、IFN-γ、IgG改变情况及小鼠肝肺的病理学检测。
结果：①FLK高剂量组能明显增加小鼠胸腺指数(P<0.05)；②FLK高剂量组CD4+T细胞数显著升高(P<0.01,P<0.05)；CD8+各组之间比较差异无显著性(P>0.05)；模型组CD4+/CD8+比值显著降低,其差异有显著性(P<0.01),FLK高剂量组明显减轻CD4+/CD8‘比值下降,其差异有显著性(P<0.01)；③FLK高剂量组增加小鼠结核模型血浆IFN-γ和IgG水平(P<0.05)。④与抗痨西药组比较,经病理学组织学观察,肺痨康加抗痨药组肝脏多发性坏死病变明显减轻。结论：①肺痨康治疗结核病具有免疫调节抗结核的作用。②肺痨康和西药组合用对结核小鼠模型的治疗有协同增效的作用；③肺痨康对抗痨化学疗法所致肝损害有一定的保护作用。
Objective To study the effect of FeiLao-kang (FLK) on the changes of immunological indices of mouse tuberculosis model and provide the research evidence of FLK for the treatment of tuberculosis.
Methods After the animal model establishment, the mice were randomly divided into the following groups:high-dose group of FLK, moderate-dose group of FLK, group of RFP, group of INH, group of FLK add RFP, group of FLK add INH and a control group. The RFP capsules, FLK, NS were given separately for 28 days. To observe the changes of thymus index, T-lymphocyte subsets, IFN-y, IgG in experiment mouse.
Result①The high-dose group of FLK to a marked increase in thymus index of mice (P<0.05);②The number of CD4+ T cells increased significantly in high dose group of FLK (P<0.01, P<0.05); the number of CD8+ in each group Comparison between the difference was not significant (P> 0.05); The ratio of CD4+ /CD8+ were significantly in lower model group, the difference was significant (P<0.01), The ratio of CD4+ /CD8+ significantly reduce the decreased in high-dose group of FLK,the difference was significant (P<0.01);③the serum levels of IFN-y and IgG under the groups treated with high-dose FLK was increased (P<0.05).④To compare with the latter line antituberculosis drug group:to observe by the result of pathological histology, liver multiple thanatosis had lessened in FeiLao-kang group and the latter line antituberculosis drug group.
Conclusion①FLK show definite immuno regulatory and anti-tuberculosis effects.②In the animal experiment, we can get good therapeutic efficacy from using FeiLao-kang group to treat TB.③FeiLao-kang had the certain protecting effect on liver pathologic lesion induced by antiphtisy and chemotherapy.
引文
[1]Chan ED, Iseman MD. Current medical treatment for tuberculosis. BMJ,2002,325, (30):1282-1286.
[2]娄加陶,周哗,吴传勇等.重组结核分枝杆菌多表位肽的免疫原性研究[J].临床军医杂志,2007,35(2)：162-124.
[3]宋小冬,任彦薇,张宏娟等.初治菌阳肺结核患者T淋巴细胞亚群测定与预后关系的临床意义[J].中国防痨杂志,2002,24(4)：185-187.
[4]汤红明,刘君炎,高立芬.IFN-γ与TNF联合治疗结核菌感染小鼠疗效及机理的研究[J].免疫学杂志,2001,17(6)：457-459.
[5]Mohammed KA ,Nasreen N.[J].ward MJ Am J Respir Crit CareMed,1999,19(5Pt,1):1653-1659.
[6]AmeixaC,Friedll and JS.[J].InfectImmun,2001,69(4):2470-2476.
[7]rikscnU,HattenhorstU,SchnciderPetal.[J].Blood,1998,(92)4:1097-11033.
[8]唐神结,综述,肖和平,审校.结核病免疫研究进展[J].国外医学内科学分册.2002,29(9)
[9]阎邦首.中草药抗结核作用的实验方法[J].中华结核病和呼吸系统疾病杂志1980.3(2)123.
[10]徐书显.赵进沛.刘卫.等复方中药对小鼠免疫器官和体质量的影响
[J].现代中西医结台杂志,2001,(4)：710.
[11]申金贵,叶品良,王帅等.肺痨康对小鼠结核病模型的免疫指标观察[J].浙江中医药大学学报,2010,·34(1)：48-49.
[12]涂叔云.卞如耀,陈修主编,药理实验方法学[M]：第二版,北京人民卫生出版社.1994.1.1392.
[13]叶品良,卢润生,黄秀深等.肺痨康治疗肺结核69例[J].江西中医药.2009,40(2)：33.
[14]刘婷婷.叶品良.王帅等.“肺痨康”对耐多药结核分枝杆菌抑菌效力的体外研究[J].光明中医,2008(10)：1453.
[15]陈文杰.猫爪草抗结核的研究现状[J].中医药管理杂志,2006,10(14)： 69.
[16]高富红,孙健,吴国娟.天花粉蛋白抗肿瘤作用机理研究概况[J].动物医学进展,2005,26(11)：5-7.
[17]叶品良,卢润生,黄秀深等.肺痨康治疗耐药性肺结核69例[J].江西中医药,2009,40(2)：33.
[18]张瑞梅,高春景,胡凯.肺泰胶囊配合西药治疗耐药性肺结核115例[J].陕西中医,2006,27(12)：1470-1472.
[19]肖志坚,崔秀琴,陶五昌等.耐多药肺结核患者T淋巴细胞亚群测定[J].中华结核和呼吸杂志,1998,(21)：434.
[20]林存智.朱新红,邓凯等.中药肺腑汤治疗耐药性肺结核病的临床研究[J].中华中医药学刊,2008：26(11)：2472-2473.
[21]李晓红,李影,陈亦洋.耐多药肺结核的中西医结合认识[J].中国社区医师,2006,8(137)：55.
[22]李涛,胡洪民.浅述药性理论的物质基础[J].国医论坛,2001,(2)：47.
[23]于培明,田智勇.甘味药的药性理论及其配伍探讨[J].时珍国医国药,2005,(1)：77-78.
[24]向阳,易晋华等.肺结核的中医治疗现状及展望[J].浙江中西医结合杂志，2001(11)4,261-264.
[25]JOHNSON B J, ESTRADA I, SHEN Z, et al. Differential gene expression in response to adjunctive recombinant human interleukin-2 immunot herapy inmutidny-resistant tuberculosis patients [J]. Infect Immune,1998,66:2426.
[26]张涛,柳朝阳,王建杰,等.肉苁蓉总苷对D—半乳糖所致衰老模型小鼠免疫功能的影响[J].中国老年学杂志,2004；24(5)：441-2.
[27]邓国防,雷建平.结核病与相关免疫细胞和细胞因子[J].中国防痨杂志2008；5(30)：654-954.
[28]Flgnn JL, Chun J,Triebold KJ, et al. An essential role for inter- feron in resistance to mycobacterium tuberculosis infection [J]. J Exp Med,1993,178(6):2249-2254.
[29]Flesch I, Kaufmann SH. Mycobacterial growth inhibition by interferon-gamma-activated bone marrow macrophages and differential susceptibility among strains of Mycobacterium tuberculosis[J]. The Journal of Immunology,1987,138(12):4408-4413.
[30]Cooper AM, Dalton DK, Stewart TA, et al. Disseminated tuberculosis in interferon gamma gene-disrupted mice[J]. Journal of Experimental Medicine,178: 2243-2247.
[31]Flynn JL, Chan J, Triebold KJ, et al. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection[J]. Journal of Experimental Medicine,1993,178:2249-2254.
[32]Newport MJ, Huxley CM, Huston S, et al. A Mutation in the Interferon-y-Receptor Gene and Susceptibility to Mycobacterial Infection[J]. The New England Journal of Medicine,1996,335:1941-1949.
[33]华树成,许力军,吕晓红等.IFN-y治疗结核的动物实验研究[J].中国老年学杂志2002年5期035.
[34]Tchou-WongK M,H arkinT J,ChiC,eta 1. [J]AmJ R esPlrC ritC areM ed,1997, 156(6):1996-2002.
[35]Fenton MJ, Vermeulen MW. Immunopathology of Tuberculosis:Roles of Macrophages and Monocytes[J]. Infection and Immunity,1996,64(3):683-690.
[36]Schluger NW, Rom WN. The Host Immune Response to Tuberculosis[J]. Am J Respir Crit Care Med,1998,157:679-691.
[37]余绍珍,王庭贵,李作勇,等.活动性肺结核病人治疗前、后外周血T淋巴细胞亚群变化及其临床意义探讨[J].中华结核和呼吸杂志,1992；15(5)：311.
[38]秦菁,姚一中,杨德燕,等.肺结核患者自然杀伤细胞活性和T淋巴细胞亚群的测定[J].中华结核和呼吸杂志,1990；13(4)：209.
[39]旷寿金,周汉昭.儿童结核病患者外周血淋巴细胞亚群变化初步观察[J].湖南医学,1991；8(6)：32.
[40]华树成,许力军,吕晓红.等.IFN-γ治疗结核的动物模型实验研究[J].中国老年学杂志.2002.22(5)：391.393.
[41]龚非力.医学免疫学[M].北京：科学出版社,2000：33—34.
[42]张立群,马伟路抗结核保护性免疫机制研究的若干进展[J].中华呼吸与结 核杂志,2000,23(3)：183-185.
[43]谢惠安.阳国太.林善梓等主编.现代结核病学[M].人民卫生出版社。2000：148.
[44]于虹.中药双向性作用及其相关因素探讨[J].中医药学刊,200.3,21(4)：637.
[45]陈慧敏. 蛤蚧的药用研究概述[J].中草药,1995,26,(5)：268-269.
[46]龚千峰.蛤蚧不同部位的药理作用[J].中药材,1998,21(4)：196.
[47]刘咏梅：刘波,王金凤,等.北沙参粗多糖的提取及对阴虚小鼠的免疫调节作用[J].中国生化药物杂质,2005,26(4)：224-225
[48]郭峰,刘小平,徐瑛.天花粉对小鼠艾氏腹水癌的疗效和对红细胞免疫功能的影响[J].中西医结合杂志,1989；9：418.
[49]江秀娥,裴洪烈.抗结核药物致严重肝损害的诊断及治疗[J].天津医药.2003；30(5)：303-304.
[50]Qu Yw Guyl. Zhao GD. M echanism and Preuention of Liver Dysfunction by Antituberculosis Drugs[J]. J Chin Antituberculosis,2001; 23(1):56-56.
[51]Tan Yk. Liver Dysfunction by Drugs[J]. J Chin Antituberculosis,2002; 24 (1):41-43
[52]吴静,张春梅.抗结核药物对肺结核患者肝功能的影响及防治[J].中国临床医药研究杂志.2008年总第200期,39-40.
[1]林志刚,陈彬,汪晓丹等,免疫治疗在复治涂阳肺结核病人治疗的观察[J]临床肺科杂志,200712(6)：626-627.
[2]唐神结张忠顺肺结核病[M].上海科学技术文献出版社2004年7月.
[3]彭卫生,王英年,肖成志,新编结核病学[M].北京：中国医学科技出版社1999.65.
[4]谢惠安,阳郭太,林善梓,等.现代结核病学[M].北京：人民卫生出版社,2000：135.
[5]谢惠安,阳国太,林善祥,等.现代结核病学[M].北京：人民卫生出版社,2000,146-147.
[6]唐神德,肖和平.细胞因子网络与结核病[J].中华结核与呼吸杂志,2001,9(24)：571-573.
[7]Sung CH Kim Hs ParkTK.et al.Leespressed interlukin-12hut not IL-18production in response to pulmonaty tuberculosis [J].Infect Immun2000,6 (8):4477-4484.
[8]杨国儒,韩国然,孙永昌.免疫力抑制剂相关肺结核[J].中华结核与呼吸杂志,1998,6：380.
[9]刘清蒙,赵静主编.现代结核病学[M]. 贵阳：贵州科学技术出版社,1998：1218,3152.
[10]何礼贤.免疫损害患者并发肺结核的若干临床问题[J].中华结核和呼吸杂志,1996；19(1)：56.
[11]Thilothamal N.Does BCG vaccine prevent tuberculosis meningitis?[J].Archives of Disease in Childhood,1996,74(3):144.
[12]王黎霞,杨华林.西部地区结核病控制工作面临的挑战与机遇[J].中国防痨杂志,2001,24(8)：10.
[13]李志惠,杨永辉,宋海亭.肺结核患者体内细胞因子水平的动态变化与耐药关系的研究[J].医学动物防制.2006,22(9)：654-655.
[14]Caterll, Swain SL. Single Cell analyses of cytokine production. Curropin Immunol,1997,9(3):177-182.
[15]张河川.30例肺结核患者心理健康及生活事件的配对研究[J].中国校医2000,14(14)：253-255.
[16]殷大奎.开创结核病防治工作的新局面[J].中华结核和呼吸杂志,1996；19(6)：323326.
[17]严碧涯.严峻的形势和我们共同的任务[J].中华结核和呼吸杂志,1994；17(5)：266.
[18]周焱 中国医药报3.7；3.9
[19]徐苗、罗永艾、王国治.结核病免疫研究进展[J].国外医学内科学分册2004年12月第31卷第12期52.
[2]娄加陶,周哗,吴传勇等.重组结核分枝杆菌多表位肽的免疫原性研究[J].临床军医杂志,2007,35(2)：162-124.
[3]宋小冬,任彦薇,张宏娟等.初治菌阳肺结核患者T淋巴细胞亚群测定与预后关系的临床意义[J].中国防痨杂志,2002,24(4)：185-187.
[4]汤红明,刘君炎,高立芬.IFN-γ与TNF联合治疗结核菌感染小鼠疗效及机理的研究[J].免疫学杂志,2001,17(6)：457-459.
[5]Mohammed KA ,Nasreen N.[J].ward MJ Am J Respir Crit CareMed,1999,19(5Pt,1):1653-1659.
[6]AmeixaC,Friedll and JS.[J].InfectImmun,2001,69(4):2470-2476.
[7]rikscnU,HattenhorstU,SchnciderPetal.[J].Blood,1998,(92)4:1097-11033.
[8]唐神结,综述,肖和平,审校.结核病免疫研究进展[J].国外医学内科学分册.2002,29(9)
[9]阎邦首.中草药抗结核作用的实验方法[J].中华结核病和呼吸系统疾病杂志1980.3(2)123.
[10]徐书显.赵进沛.刘卫.等复方中药对小鼠免疫器官和体质量的影响
[J].现代中西医结台杂志,2001,(4)：710.
[11]申金贵,叶品良,王帅等.肺痨康对小鼠结核病模型的免疫指标观察[J].浙江中医药大学学报,2010,·34(1)：48-49.
[12]涂叔云.卞如耀,陈修主编,药理实验方法学[M]：第二版,北京人民卫生出版社.1994.1.1392.
[13]叶品良,卢润生,黄秀深等.肺痨康治疗肺结核69例[J].江西中医药.2009,40(2)：33.
[14]刘婷婷.叶品良.王帅等.“肺痨康”对耐多药结核分枝杆菌抑菌效力的体外研究[J].光明中医,2008(10)：1453.
[15]陈文杰.猫爪草抗结核的研究现状[J].中医药管理杂志,2006,10(14)： 69.
[16]高富红,孙健,吴国娟.天花粉蛋白抗肿瘤作用机理研究概况[J].动物医学进展,2005,26(11)：5-7.
[17]叶品良,卢润生,黄秀深等.肺痨康治疗耐药性肺结核69例[J].江西中医药,2009,40(2)：33.
[18]张瑞梅,高春景,胡凯.肺泰胶囊配合西药治疗耐药性肺结核115例[J].陕西中医,2006,27(12)：1470-1472.
[19]肖志坚,崔秀琴,陶五昌等.耐多药肺结核患者T淋巴细胞亚群测定[J].中华结核和呼吸杂志,1998,(21)：434.
[20]林存智.朱新红,邓凯等.中药肺腑汤治疗耐药性肺结核病的临床研究[J].中华中医药学刊,2008：26(11)：2472-2473.
[21]李晓红,李影,陈亦洋.耐多药肺结核的中西医结合认识[J].中国社区医师,2006,8(137)：55.
[22]李涛,胡洪民.浅述药性理论的物质基础[J].国医论坛,2001,(2)：47.
[23]于培明,田智勇.甘味药的药性理论及其配伍探讨[J].时珍国医国药,2005,(1)：77-78.
[24]向阳,易晋华等.肺结核的中医治疗现状及展望[J].浙江中西医结合杂志，2001(11)4,261-264.
[25]JOHNSON B J, ESTRADA I, SHEN Z, et al. Differential gene expression in response to adjunctive recombinant human interleukin-2 immunot herapy inmutidny-resistant tuberculosis patients [J]. Infect Immune,1998,66:2426.
[26]张涛,柳朝阳,王建杰,等.肉苁蓉总苷对D—半乳糖所致衰老模型小鼠免疫功能的影响[J].中国老年学杂志,2004；24(5)：441-2.
[27]邓国防,雷建平.结核病与相关免疫细胞和细胞因子[J].中国防痨杂志2008；5(30)：654-954.
[28]Flgnn JL, Chun J,Triebold KJ, et al. An essential role for inter- feron in resistance to mycobacterium tuberculosis infection [J]. J Exp Med,1993,178(6):2249-2254.
[29]Flesch I, Kaufmann SH. Mycobacterial growth inhibition by interferon-gamma-activated bone marrow macrophages and differential susceptibility among strains of Mycobacterium tuberculosis[J]. The Journal of Immunology,1987,138(12):4408-4413.
[30]Cooper AM, Dalton DK, Stewart TA, et al. Disseminated tuberculosis in interferon gamma gene-disrupted mice[J]. Journal of Experimental Medicine,178: 2243-2247.
[31]Flynn JL, Chan J, Triebold KJ, et al. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection[J]. Journal of Experimental Medicine,1993,178:2249-2254.
[32]Newport MJ, Huxley CM, Huston S, et al. A Mutation in the Interferon-y-Receptor Gene and Susceptibility to Mycobacterial Infection[J]. The New England Journal of Medicine,1996,335:1941-1949.
[33]华树成,许力军,吕晓红等.IFN-y治疗结核的动物实验研究[J].中国老年学杂志2002年5期035.
[34]Tchou-WongK M,H arkinT J,ChiC,eta 1. [J]AmJ R esPlrC ritC areM ed,1997, 156(6):1996-2002.
[35]Fenton MJ, Vermeulen MW. Immunopathology of Tuberculosis:Roles of Macrophages and Monocytes[J]. Infection and Immunity,1996,64(3):683-690.
[36]Schluger NW, Rom WN. The Host Immune Response to Tuberculosis[J]. Am J Respir Crit Care Med,1998,157:679-691.
[37]余绍珍,王庭贵,李作勇,等.活动性肺结核病人治疗前、后外周血T淋巴细胞亚群变化及其临床意义探讨[J].中华结核和呼吸杂志,1992；15(5)：311.
[38]秦菁,姚一中,杨德燕,等.肺结核患者自然杀伤细胞活性和T淋巴细胞亚群的测定[J].中华结核和呼吸杂志,1990；13(4)：209.
[39]旷寿金,周汉昭.儿童结核病患者外周血淋巴细胞亚群变化初步观察[J].湖南医学,1991；8(6)：32.
[40]华树成,许力军,吕晓红.等.IFN-γ治疗结核的动物模型实验研究[J].中国老年学杂志.2002.22(5)：391.393.
[41]龚非力.医学免疫学[M].北京：科学出版社,2000：33—34.
[42]张立群,马伟路抗结核保护性免疫机制研究的若干进展[J].中华呼吸与结 核杂志,2000,23(3)：183-185.
[43]谢惠安.阳国太.林善梓等主编.现代结核病学[M].人民卫生出版社。2000：148.
[44]于虹.中药双向性作用及其相关因素探讨[J].中医药学刊,200.3,21(4)：637.
[45]陈慧敏. 蛤蚧的药用研究概述[J].中草药,1995,26,(5)：268-269.
[46]龚千峰.蛤蚧不同部位的药理作用[J].中药材,1998,21(4)：196.
[47]刘咏梅：刘波,王金凤,等.北沙参粗多糖的提取及对阴虚小鼠的免疫调节作用[J].中国生化药物杂质,2005,26(4)：224-225
[48]郭峰,刘小平,徐瑛.天花粉对小鼠艾氏腹水癌的疗效和对红细胞免疫功能的影响[J].中西医结合杂志,1989；9：418.
[49]江秀娥,裴洪烈.抗结核药物致严重肝损害的诊断及治疗[J].天津医药.2003；30(5)：303-304.
[50]Qu Yw Guyl. Zhao GD. M echanism and Preuention of Liver Dysfunction by Antituberculosis Drugs[J]. J Chin Antituberculosis,2001; 23(1):56-56.
[51]Tan Yk. Liver Dysfunction by Drugs[J]. J Chin Antituberculosis,2002; 24 (1):41-43
[52]吴静,张春梅.抗结核药物对肺结核患者肝功能的影响及防治[J].中国临床医药研究杂志.2008年总第200期,39-40.
[1]林志刚,陈彬,汪晓丹等,免疫治疗在复治涂阳肺结核病人治疗的观察[J]临床肺科杂志,200712(6)：626-627.
[2]唐神结张忠顺肺结核病[M].上海科学技术文献出版社2004年7月.
[3]彭卫生,王英年,肖成志,新编结核病学[M].北京：中国医学科技出版社1999.65.
[4]谢惠安,阳郭太,林善梓,等.现代结核病学[M].北京：人民卫生出版社,2000：135.
[5]谢惠安,阳国太,林善祥,等.现代结核病学[M].北京：人民卫生出版社,2000,146-147.
[6]唐神德,肖和平.细胞因子网络与结核病[J].中华结核与呼吸杂志,2001,9(24)：571-573.
[7]Sung CH Kim Hs ParkTK.et al.Leespressed interlukin-12hut not IL-18production in response to pulmonaty tuberculosis [J].Infect Immun2000,6 (8):4477-4484.
[8]杨国儒,韩国然,孙永昌.免疫力抑制剂相关肺结核[J].中华结核与呼吸杂志,1998,6：380.
[9]刘清蒙,赵静主编.现代结核病学[M]. 贵阳：贵州科学技术出版社,1998：1218,3152.
[10]何礼贤.免疫损害患者并发肺结核的若干临床问题[J].中华结核和呼吸杂志,1996；19(1)：56.
[11]Thilothamal N.Does BCG vaccine prevent tuberculosis meningitis?[J].Archives of Disease in Childhood,1996,74(3):144.
[12]王黎霞,杨华林.西部地区结核病控制工作面临的挑战与机遇[J].中国防痨杂志,2001,24(8)：10.
[13]李志惠,杨永辉,宋海亭.肺结核患者体内细胞因子水平的动态变化与耐药关系的研究[J].医学动物防制.2006,22(9)：654-655.
[14]Caterll, Swain SL. Single Cell analyses of cytokine production. Curropin Immunol,1997,9(3):177-182.
[15]张河川.30例肺结核患者心理健康及生活事件的配对研究[J].中国校医2000,14(14)：253-255.
[16]殷大奎.开创结核病防治工作的新局面[J].中华结核和呼吸杂志,1996；19(6)：323326.
[17]严碧涯.严峻的形势和我们共同的任务[J].中华结核和呼吸杂志,1994；17(5)：266.
[18]周焱 中国医药报3.7；3.9
[19]徐苗、罗永艾、王国治.结核病免疫研究进展[J].国外医学内科学分册2004年12月第31卷第12期52.