肝应春与过敏免疫相关性的理论和实验研究

【作者】 秦子舒；

【导师】 马淑然；

【作者基本信息】 北京中医药大学 ， 中医基础理论， 2012， 硕士

【副题名】四季变化对过敏免疫的影响

【摘要】 中医学“天人相应”理论认为人体五脏功能的变化与自然气候的变化是一致的,是中医学的重要理论基础。“肝应春”是“天人相应”理论中的重要部分,是指肝与春季的气候变化具有同步振荡和协同关系。中医学对于五脏功能的认识与西医学对于机体各系统的认识之间存在着很多相通的地方,这为从中西医结合的角度研究脏腑调控理论提供了必要的切入点,如中医的风邪和现代医学的过敏原就有很多相似处。本课题组在“天人相应”的研究中,已经对“心应夏”、“肾应冬”和“肺应秋”都有了一定的理论和实验研究,而“肝应春”的实验研究尚属空白。通过对中医“肝应春”的理论和实验研究,能深化对中医肝藏象本质的认识,更好的为临床服务。1目的本研究从现代医学过敏免疫角度阐述中医“肝应春”理论的免疫学内涵,为临床过敏性疾病的防治提供理论和实验依据。2方法2.1理论研究本研究采用文献资料法和逻辑分析法,对历代关于肝应春理论进行系统梳理。2.2实验研究2.2.1实验动物健康SD雄性大鼠96只,清洁级,体重150-170g,分别于2010年春分、夏至、秋分、冬至(简称二分、二至)前四十天购入。随机分为生理组、伪手术组和手术组,每组各8只。自然光照,室温饲养。手术组和伪手术组分别于二分、二至前一个月施行造模手术,与生理组在相同条件下饲养到二分、二至当日晚8：00以后处死取材。2.2.2检测方法血清免疫应答相关物质：IgE、IgG、TNF-α、IL-13:采用ELISA法。血清Mel：采用ELISA法。胸腺指数、脾脏指数直接称重。2.2.3统计分析：统计软件：SPSS11.7,数据表示：均数±标准差,检验方法：单因素方差分析(One-WayANOVA),以P<0.05有显著差异,P<0.01有极显著差异。3结果3.1理论研究结果(1)肝应春理论是在天人相应理论指导下,通过取象比类为思维模式,以阴阳五行为理论框架,以气理论为肝与春联系的中介,逐步形成的一种时脏相应理论。(2)中医“肝应春”理论的特点是：肝与春季光照相应；肝与春季风气相应。春季自然界阳气生发,风气渐盛,人体肝气顺应自然生发特点,疏泄功能旺盛,易产生内风,外风引动内风则春季多发与风邪相关的疾病(过敏性疾病等)。(3)风邪除在肝脏所主的季节对人体造成伤害外,还在不同季节伤害相应之脏,并且常兼时令主气。如夏季风热伤心,秋季风燥伤肺,冬季风寒伤肾等,这可能是风邪致病(过敏性疾病)不同季节发作的生理病理基础。(4)过敏性疾病属于西医范畴,但它和中医的风邪所导致的疾病一样,具有起病急,发病快,易反复发作,部位多变,游走不定和瘙痒难耐的特点。春季多风,此时也是过敏性疾病的高发季节,并且过敏原与风邪具有明显的相关性。这为临床从风论治过敏性疾病提供了理论基础。(5)中医在临床上治疗过敏性疾病的过程中发现从肝论治和从风论治都具有明显的疗效。3.2实验研究结果3.2.1季节变化及摘除松果腺对免疫器官的影响(1)胸腺指数：生理组胸腺指数具有春季>夏季>秋季>冬季的趋势,与春夏相较,秋冬具有极显著差异(P<0.01)；手术组与同一季节生理组相比,春夏呈下降趋势,秋冬呈上升趋势,春分、秋分时有显著差异(P<0.05)。(2)脾脏指数：生理组脾脏指数具有夏季>春季>秋季>冬季的趋势,与冬至相比,春分、夏至有极显著差异(p<0.01),秋分差异显著(P<0.05)；手术组与同一季节生理组相比无显著差异,冬春略低,夏秋呈上升趋势。3.2.2季节变化及摘除松果腺对血清免疫因子的影响(1)血清TNF-α:生理组血清TNF-α含量具有冬季>秋季>夏季>春季的趋势,与春分和夏至相较,秋分和冬至具有极显著差异(P<0.01)；手术组与同一季节生理组相比,均无显著差异(P>0.05),但较当季生理组都有升高的趋势；三组的季节节律始终表现为：冬季>秋季>夏季>春季的趋势,且其含量冬季明显高于其他三季。(2)血清IL-13：生理组血清IL-13含量具有冬季>夏季>秋季>春季的趋势,春分、夏至、秋分与冬至比较,均有极显著性差异(P<0.01)；手术组与同一季节生理组相比,秋分时有极显著差异(P<0.01),各季节较生理组都有升高的趋势。虽然伪手术组和手术组的血清IL-13含量季节节律有所改变,但冬季依然明显高于其他三季。(3)血清IgG：生理组血清IgG含量具有夏季>春季>冬季>秋季的趋势,春分、秋分、冬至与夏至相比,有极显著差异(P<0.01)。秋分、冬至与春分相比,也有极显著差异(P<0.01)；手术组与同一季节生理组相比,冬至时有显著差异(P<0.05),各季节较生理组都有升高的趋势；三组的季节节律始终表现为：春夏明显高于秋冬的特点。(4)血清IgE：生理组血清IgE含量具有冬季>春季>夏季>秋季的趋势,与春分相比,夏至、秋分有极显著差异(P<0.01),与夏至相比,秋分、冬至也有极显著差异(P<0.01),秋分和冬至相比亦有极显著差异(P<0.01)；手术组与同一季节生理组相比,秋分时差异极为显著(P<0.01),较当季生理组都有升高的趋势；三组的季节节律始终表现为：春夏明显高于秋冬的特点。3.2.3季节变化及摘除松果腺对血清褪黑素的影响生理组血清Mel含量具有春季>冬季>秋季>夏季的趋势,夏至、秋分与春分比较,有显著性差异(P<0.05),血清Mel春季为的含量最高；同季节手术组血清Mel含量较生理组明显降低,以春分为差异最显著(P<0.05)；手术组血清Mel四季含量并无明显差异,与生理组的节律性明显不同。4结论(1)现代医学的过敏免疫属于中医肝功能的范畴。运用文献整理法和逻辑分析法,以春季风气通于肝,春季为过敏性疾病的高发季节为依据,从过敏原属于中医风邪范畴的角度可推理出现代医学的过敏免疫属于中医肝功能的范畴。(2)临床上在治疗春季高发的过敏性疾病时可从“肝”从“风”论治。通过临床上关于过敏性疾病的中医治疗和所用方药可知从内因的肝和外因的风对过敏性疾病的治疗行之有效。(3)血清IgG、IgE可能与春季高发的过敏性疾病有关,而血清TNF-α和IL-13可能与冬季高发的过敏性疾病有关。在选择的四组过敏免疫指标中血清IgG、IgE都有春季明显升高的趋势,而血清TNF-α和IL-13则都有冬季明显升高的趋势。(4)松果腺及褪黑素对过敏免疫具有调节作用。具体表现为松果腺对机体血清免疫因子具有抑制作用,而对免疫器官的发育具有调节作用；褪黑素对机体的免疫系统具有复杂的调节作用。(5)中医肝应春的内涵与松果腺褪黑素及机体过敏免疫具有相关性。更多还原

【Abstract】 In TCM theory,"Correspondence between Man and Nature" which is an important theoretical basis In traditional Chinese Medicine means man and nature is an integrated whole."Liver correspondence to Spring" which is an important part of "Correspondence between Man and Universe"Refers to the liver and the spring climate change with synchronous oscillations and collaborative relationship.there is many similarities understanding between Chinese medicine for five organs system and the respiratory system, motor system, genitourinary system, digestive system, circulatory system of Western Medicine,Such as the wind evil of traditional Chinese Medicine and the allergen of modern medicine.The combination of traditional Chinese and Western medicine research internal control theory provides a good bond and bridge.The research group of "correspondence between man and nature" in the study, has been on the "kidney correspondence to winter","lung correspondence to autumn" and "heart correspondence to summer" has certain theoretical and experimental studies, but "liver correspondence to spring" is still belongs to blank.On the theory research of "liver correspondence to spring" contributes to deepening on the understanding of liver function in seasonal changes,is important clinical guidance to occur allergic disease prevention and treatment in the spring,and deepen the understanding of the essence of the liver.1ObjectiveThrough literature this study found that spring is the season of high incidence of allergic disease. we Conduct the four seasons change on allergy of immunology experimental study,begin with the relationship of wind evil and allergic disease.From the allergy of immunology in modern medicine perspective to explain the essence of the traditional Chinese medicine "liver correspondence to spring".2Methods2.1Theoretical methodsThis study which used the method of literature and logical analysis, to allergic diseases occur in the spring you as the clue, correlation of the wind evil of traditional Chinese medicine and the allergy of immunology in modern medicine as a starting point discuss liver and allergic of immune correlation.In order to find the modern medicine material basis of liver in traditional Chinese Medicine.2.2Experimental methods2.2.1Experimental animalsExperimental animals:twenty-four SD male rats, clean,weighted150-170g, brought forty days before vernal equinox, summer solstice, autumnal equinox and winter solstice in2010, were randomly divided into three groups:normal group, fake group and operation group (pinealectomy group), there were eight rats in every group. All rats received natural light, ate and drank freely, and were controlled under certain room temperature. Fake group and operation group are operated a month before vernal equinox, summer solstice, autumnal equinox and winter solstice. All the rats would be raised before being beheaded at8o’clock at night in vernal equinox, summer solstice, autumnal equinox and winter solstice.2.2.2Test methodsSerum immune response related to substance lgE, lgG, TNF-A.IL-13:using ELISA method.Serum Mel:using ELISA method. The thymus index, spleen index direct weighing.2.2.3Analysis method:All the data were showed by mean±standard error. The differences of groups were tested by SPSS11.0. The values were calculated with Duncan’s multiple range test or Student’s test. P<0.05meant obvious difference.3Results3.1Results of theoretical study (1)From research of "Liver correspondence to Spring" by history of Chinese medicine,it can be found that liver function will be appeared rhythmic changes in the spring,thus affecting the whole human body function. Deep understanding of liver function of rhythm characteristics have the profound significance for ome seasonal incidence of disease prevention and treatment.(2)Allergic diseases belongs to the category of Western medicine,but it has a rapid onset, rapid onset, easy to repeated attacks, parts move uncertain and changeable, itching intolerable characteristics,the same of Chinese medicine diseases caused by pathogenic wind.(3)The onset of allergic disorders is allergen invasion causes the allergic immune response process, while the majority of allergic diseases predominate in the allergic immune index IgE.4.Chinese medicine in clinical treatment of allergic diseases were found during treatment from liver and dealing with the wind has apparent curative effect.3.2Results of experiments3.2.1Influence on immune organs by seasonal variation and extracting pinealectomy(1)Thymus index:Physiological group had trend spring>summer>autumn>winter, there was a very significant difference (P<0.01) in autumn and winter compared with in spring and summer;In the same season,there was a significant difference (P<0.05) and showing the trend of content descending in spring and summer and rising in autumn and winter that operation group compared with physiology group.(2)Spleen index:Physiological group had the trend of content summer>spring>autumn>winter,there was a very significant difference (P<0.01) in spring and summer compared with in winter,there was a significant difference (P<0.05) in autumn compared with in winter;In the same season,there was no significant difference but showing the trend of content descending in spring and winter and rising in autumn and summer that operation group compared with physiology group.3.2.2Influence on immune factors in serum by seasonal variation and extracting pinealectomy(1) TNF-α in Serum:Physiological group had the trend of content winter>autumn>summer>spring, there was a very significant difference (P<0.01) in autumn and winter compared with in spring and summer;In the same season,there was no significant difference but showing the the trend of content rising that operation group compared with physiology group.Three groups of seasonal rhythm always embodied the trend winter>autumn>summer>spring,and the content was highest in winter compared with other season.(2)IL-13in Serum:Physiological group had the trend of content winter>summer>autumn>spring, there was a very significant difference (P<0.01) in spring and summer and autumn compared with in winter;In the same season,there was a very significant difference (P<0.01) in autumn and showing the the trend of content rising that operation group compared with physiology group.Although the seasonal rhythm of the content IL-13of pseudo operation group and operation group was changed,the content was highest in winter compared with other season.(3)IgG in Serum:Physiological group had the trend of content summer>spring>winter>autumn, there was a very significant difference (P<0.01) in spring and autumn and winter compared with in summer;ln the same season,there was a significant difference (P<0.05) in winter and showing the the trend of content rising that operation group compared with physiology group;Three groups of seasonal rhythm was always embodied in spring and summer higher than in autumn and winter.(4)IgE in Serum:Physiological group had the trend of content winter>spring>summer>autumn,there was a very significant difference (P<0.01) in summer and autumn compared with in spring,and was a very significant difference (P<0.01) in autumn and winter compared with in summer,and was a very significant difference (P<0.01) in autumn compared with in winter; In the same season,there was a very significant difference (P<0.01) in autumn and showing the the trend of content rising that operation group compared with physiology group;Three groups of seasonal rhythm was always embodied in spring and summer higher than in autumn and winter.3.2.2Influence on by seasonal variation and extracting pinealectomyMel in serum of Physiological group had the trend of content winter>spring>summer>autumn,there was a significant difference(P<0.05)in autumn compared with in spring,and the content in spring is highest than other season; In the same season,there was a significant difference (P<0.05) in spring and showing the the trend of content descending that operation group compared with physiology group;Operation group Mel in serum content did not differ significantly between seasons, and physiological group rhythm was significantly different.4Conclusions(1)According to "Literature review method" and "Logical analysis" and allergen belonging to the Chinese wind evil category,by spring high incidence of allergic disease as carrier,we can deduce that The modern medicine allergic immune belongs to the traditional Chinese medicine liver function category.(2)In clinical we can cure allergic diseases which is high incidence in spring. from the liver and the wind.(3)In the six index of allergy and Immunology,serum IgG and IgE, thymus and spleen index has increased in spring,so the four index are closely related with the allergic diseases which is high incidence in spring.TNF-a in Serum and IL-13in Serum are closely related with the allergic diseases which is high incidence in winter.(4)The pineal and Mel has a modulatory role on allergen immunotherapy,The specific performance is that the pineal have inhibition to serum immune factors, and have complex regulatory role to the immune organs.Mel has a complex regulatory role to the body’s immune system.(5)The connotation of "Liver correspondence to Spring" is related to the pineal and Mel and Allergic immune of body更多还原