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桂枝汤证治规律及桂枝汤对大鼠体液免疫和细胞免疫干预作用的研究

The Law of Syndrome Differentiation of GuiZhiTang and Its Effect on Humoral Immunity and Cytoimmunity of Rats

【作者】 刘新亚

【导师】 朱章志;

【作者基本信息】 广州中医药大学 , 中医临床基础, 2005, 博士

【摘要】 桂枝汤是《伤寒杂病论》重点方剂之一,其临床运用特别广,演变特别多,桂枝汤及类方在经方中具有代表性意义。本文从理论和实验两方面对桂枝汤证治展开了研究。 第一部分:理论研究 一、《伤寒杂病论》对营卫理论的发挥 《伤寒杂病论》在全面继承《内经》营卫理论的基础上,紧密联系外感热病辨证论治的实践,从六经生理、病理和治法的角度对营卫理论加以阐述。 在六经营卫的生理方面,张仲景认识到脾胃之气调匀健旺,保证了机体阴阳相合平和,营卫气血和调流行于十二经脉。营卫发挥作用的主要场所和作用机制联系的统属地带有外行和内藏两途:由于经脉主外而太阳主表,故外行营卫之气为太阳经所统摄,也就是统属于太阳。营卫阴阳相吸,内外相谐,共司守卫肌表之职。内行之营卫主要伴血以行而藏舍于心脾,因为心主血脉,心气推动营卫循经脉运行,营虚及心则见心中烦而悸。饮食失节、饥饿等可导致脾营不足,不能充盈脾络,又使体表之营气失充。 在六经营卫的病理方面,六经病实质上是六经调节营卫气血表里出入的失常、进而导致脏腑气血津液功能紊乱所产生的病证。太阳病系太阳主司“开”的调节功能紊乱。阳明病营卫的病变为阳明主“阖”的功能失常。少阳病是病在三焦营卫,少阳主“枢”的功能失常。太阴病是太阴主“开”功能失常导致脾脏功能紊乱的病变。少阴病是少阴主“枢”功能失常,心肾受伤,营卫出入交会受阻的病变。厥阴病系厥阴主“阖”的功能失职,导致肝、心包功能失常的病变。 在营卫失调的证治方面,讨论了卫闭营郁、卫强营弱、卫弱营和、营卫俱弱、气水不和等营卫不和病证的病机及治疗。 二、桂枝汤方证辨识 桂枝汤的组方特点:桂枝辛甘而温,甘能助阳化气而益卫,辛主宣散能发汗解肌以祛卫分之邪;白芍酸苦而寒能敛阴和营;二药合用,外散内敛,调和营卫气血。生姜辛温佐桂枝发散风寒以解肌。大枣甘平佐芍药滋补阴津以养营缓急。炙甘草甘平入通脾胃以和中州,调理阴阳以补中气。 桂枝汤的功效探究:桂枝汤中五味药物相互协同,使其具有调和营卫,解肌祛邪;燮理阴阳,培补正气;扶助心阳,缓肝平木;健运脾胃,调理气血之功效。 桂枝汤方证病机实质:桂枝汤证病机是营卫俱病,营病其虚,卫病其邪;或营不病而卫虚不固。营与卫之间相对平衡失调则是其共性。卫阳不足,营卫不和才是桂枝汤证病变的性质。

【Abstract】 GuiZhi Tang is one of key decoctions of 《Treatise on Exogenous Febrile Diseases》 ,which is widely applied in clinic and has evolved into multi-forms after its formation.GuiZhi Tang and its derived formulas possess the representational significance in 《Treatise on Exogenous Febrile Diseases》. This paper researches theoretically and experimentally the treatment based on syndrome differentiation of GuiZhi Tang.Part 1 Theoretical ResearchI. Exertion of 《Treatise on Exogenous Febrile Diseases》 on nutrition qi and defensive qi theoryBased on the nutrition qi and defensive qi theory of 《Yellow Emperor Internal Classic《 , 《Treatise on Exogenous Febrile Diseases《 had elucidated ,on the basis of practical treatment based upon syndrome differentiation of exogenous febrile diseases, the theory of nutrition qi and defensive qi in the perspective of Six Meridians Physiology, Pathology and Treatment.In physiology of six meridian nutrition qi and defensive qi, ZhangZhongJing realized that sthenic and even qi of spleen and stomach guarantee Yin Yang balance of organic body and the smooth flowing of nutrient qi, defensive qi and blood in the twelve meridians. The places nutrition qi and defensive qi act on and related to consist of two aspects of outer coursing and inner coursing. Because TaiYang meridian is related to body surface, outer coursing nutrition qi and defensive qi are commanded by TaiYang meridian. Nutrition qi and defensive qi cooperate to defend the exterior through mutual attracting harmoniously. Inner coursing nutrition qi and defensive qi flows accompanied with blood and is stored in Heart and Spleen because Heart dominates blood vessel and propels the circulation of nutrition qi and defensive qi in the course of meridian. Deficient nutrition qi affecting Heart manifests in Heart vexation and palpitation. Improper diet or hungry causes spleen nutrition qi deficiency that cannot fill spleen meridian and collaterals, further fails to maintain supplement of exterior nutrient qi.In pathology of six meridian nutrition qi and defensive qi, six meridian disorder is the syndrome of abnormal regulation of six meridian on the entering and existing of nutrition qi and defensive qi from the exterior and interior, which further produces dysfunction of viscera, qi, blood, and body fluid.TaiYang disorder is its dysfunction in "opening" while YangMing nutrition qi and defensive qi disorder is their dysfunction in "closing". ShaoYang disorder takes place in triple warmer and is the dysfunction of "pivot". TaiYin disorder is dysfunction in "opening" that causes dysfunction of spleen and stomach. ShaoYin disorder is dysfunction in "pivot" and causes Heart- Kidney impairment and obstruction of nutrition qi and defensive qi entering and existing flowing. JueYin disorder is dysfunction in "closing" that causes disorder of liver and pericardium.In the treatment based upon syndrome differentiation of disharmony of nutrition qi and defensive qi, the pathology and treatment of nutrition qi and defensive qi obstruction, excessive defensive qi deficient nutrition qi, deficient defensive qi normal nutrition qi, deficient defensive qi and nutrition qi and disharmony between qi and water are discussed. I I.Characteristies of GuiZhiTangFormation feature: GuiZhi is pungent, sweet and warm. Sweet is the nature that transforms yang into qi to defend body surface, pungency dominates dispersing and perspiration to dispel evil in defensive section; BaiShao is sour, bitter and cold, which astringe yin and harmonize nutrition qi; combination of the two herbs is to dispel the exterior while astringe the internal, and is to regulate nutrition qi, defensive qi and blood . ShengJiang is pungent and warm, which insist GuiZhi in dispelling cold wind to expel evil from muscles. DaZhao is even and sweet that insist ShaoYao in nourishing yin fluid to relieve spasm.ZhiGanCao is even and sweet that is related to spleen and stomach and harmonize the middle warmer, regulating Yin and Yang to tonifing middle qi.Effect of GuiZhiTang research: coordinated by five herbs, GuiZhiTang has the effect of regulating nutrition qi and defensive qi, expelling evil from muscles, regulating yin and yang, strengthening vital qi, tonifing heart yang, relaxing liver wood, invigorating spleen and stomach and regulating qi and blood.The nature of syndromes of GuiZhiTang: Pathology is disorder in nutrition qi and defensive qi. Disorder nutrition qi produces deficient syndrome while disorder defensive qi brings exogenous evil; or yin is not ill while yang is deficient to fail to consolidate the exterior. The common property is relative imbalance between nutrition qi and defensive qi .The nature of GuiZhiTang pathology is insufficient defensive yang and disharmony between nutrition qi and defensive qi.Clinical application of GuiZhiTang: First, grasp flexibly the modification of drugs; second, amplifying its clinical application according to meridian courses; third, enlarge its application area according to visceral functional characteristics; fourth, as long as syndromes’ nature belong to GuiZhiTang syndrome category, GuiZhiTang should be applied; fifth, it should be applied regularly no matter it is applied to treat exogenous disease due to disharmony between nutrition qi and defensive qi or to treat internal miscellaneous disease due to disharmony between nutrition qi and defensive qi;sixth, associate disease differentiation with syndrome differentiation; seventh, pathology, function, actions, indications, application characteristics of decoctions that derived from GuiZhiTang through changing its components are grasped to exploit CuiZhiTang clinical area.III. discussion of GuiZhiTang in regulating nutrition qi and defensive qi GuiZhiTang in regulating nutrition qi and defensive qi lies in three aspects: One is to regulate yinand yang to exert its function according to the nature of nutrition qi and defensive qi. Two is to introduce yin from yang through regulating nutrition qi and defensive qi to acquire yin yang balance and nutrition qi and defensive qi harmony. Third is to tonify middle warmer through regulating the spleen and stomach to consolidate nutrition qi and defensive qi.Bidirection regulation of GuiZhiTang lies in that GuiZhiTang resolve partial exuberance and partial decline and remove dysfunction. Regulating nutrition qi and defensive qi and promoting circulation is one of basic methods that realize bidirection regulation of GuiZhiTang. GuiZhiTang regulates bidirectionally organic body temperature and perspiration through regulating nutrition qi and defensive qi and promoting circulation. Harmonizing spleen and stomach to insist the transformative source is the second of basic methods that realize bidirection regulation of GuiZhiTang. GuiZhiTang regulates bidirectionally abnormal blood pressure, stimulation transmitting dysfunction in large intestine and immunological dysfunction that are due to "insufficient middle qi" and "unconsolidated nutrition qi and defensive qi ".GuiZhiTang regulates spleen and stomach to regulate qi and blood and harmonize yin and yang. GuiZhi warm channel to get yang through, Shaoyao astringe yin to harmonize nutrient qi. The two drugs emphasize regulating nutrition qi and defensive qi in recovering yin yang balance. GuiZhi cooperates with GanCao, which replenish deficiency to produce yang, functioning in tonifing heart yang, reinforcing qi and blood and removing palpation. That is to treat hypo function of heart and spleen(qi deficiency or yang deficiency) to regulate bidirectionally heart rate. Shaoyao coordinates with GanCao, which astringes yin, harmonizes nutrient qi, regulates middle warmer to relax spasm. Finally, the bidirectional regulation of large intestine is acquired.IV. Classification of Syndrome Differentiation GuiZhiTang and its derived decoct i onsl.Classification of syndrome differentiation of GuiZhiTangBasic pathology of GuiZhiTang is disharmony between nutrition qi and defensive qi. Syndromes of disharmony between nutrition qi and defensive qi includes: One, TaiYang wind-stroke, deficient nutrition qi and excessive defensive qi; two, impaired vital qi and disharmony between nutrition qi and defensive qi due to delayed treatment; three, miscellaneous disease due to disharmony between nutrition qi and defensive qi; four, TaiYang wind-stroke, meridian stagnated by evil; five false application of sinking, reversed flow of qi; six, internal excessive heat, disharmony between nutritionqi and defensive qi; seven, internal deficient cold, disharmony between nutrition qi and defensive qi; eight, pregnancy reactions, disharmony between spleen and stomach. Although these eight syndrome categories are both related to disharmony between nutrition qi and defensive qi, their pathologies share common characteristics and have their distinct features perspectively. Because, there are different etiology, companied syndromes or order of applying GuiZhiTang, Which must be differentiated carefully.2.Classification of syndrome differentiation of derived decoctions (1). disharmony between nutrition qi and defensive qi; disharmony between yin and yangTaiYang sun-stroke manifested in various companied disease, which has different syndrome features: GuiZhiTang with GeGeng syndrome is used in the syndrome of TaiYang sun-stroke, stiff back and neck due to obstruct meridians; GuiZhiTang with HouPu and XinZi is used in syndrome of reverse lung qi asthma due to disharmony between nutrition qi and defensive qi; GuiZhiTang with FuZi is used in the syndrome of impaired yang due to over sweating; new added GuiZhiTang is used in the syndrome of both impairment of defensive qi and nutrition qi after sweating; GuiZhiTang with GuaLou is used in the syndrome of malnutrition tendons due to disharmony between nutrition qi and defensive qi; GuiZhiTang added with MaHuangTang or Guizhi two added with Mahuang one is used in the syndrome of tiny evil depressing the exterior after prolonged TaiYang disease; GuiZhi two added with YueBi one is used in the syndrome of tiny evil depressing the exterior with internal stagnated heat; GuiZhiTang with CaiHu is used in the syndrome of both TaiYang and ShaoYang disease. (2). Yang deficiency in thorax and heart, disharmony between yin and yangFalse treatment of TaiYang disease causes yang deficiency in thorax and heart, disharmony between yin and yang: GuiZhiTang without ShaoYao is used in the syndrome of exterior evil stagnated with yang deficiency due to false application of sinking treatment; GuiZhiTang added with FuZi getting rid of ShaoYao is used in the syndrome of excessive deficient thorax yang affecting internally Shaoyin; GuiZhiTang with GanCao is used in the syndrome of impaired heart yang due to excessive sweating method applied in TaiYang disease; GuiZhiTang with SuQi, LongGu, MuLi, getting rid of ShaoTao is used in the syndrome of released mind with exhausted yang due to excessive sweating after firing method; GuiZhiTang added with Gui is used in the syndrome of impaired yang due to reversed flow of cold qi; GuiZhiTang with LongGu, MuLi is applied in the syndrome of both deficiency of yin and yang due to insufficient essence and blood after prolong disease. (3).Deficient cold in Chong, Ren meridian, lower abdominal stasisWarming Channel Decoction is made up of GuiZhiTang, WuZhuYuTang, JiaoAiTang and MaiMenDongTang. In the Warming Channel Decoction, GuiZhi, ShengJiang, GanCao are pungent andsweet, which transform yang; BaiShao, GanCao are sour and sweet, which transform yin. While the method of nourishing yin and harmonizing yang is preserved, effect of nourishing yin, harmonizing yang and soothing nutrition qi and defensive qi by warming reinforcement through combination of these decoctions. (4).Sinking evil affecting spleen, deficient nutrition qi with abdominal painGuiZhiTang with ShaoYao is used in the deficient abdominal distention pain syndrome of disharmony between qi and blood, deficient nutrition qi and defensive qi and impaired spleen qi due to false application of sinking method in TaiYang disease; GuiZhiTang with DaiHuang is used in the excessive syndrome accompanied with deficient syndrome in the case of intestine stagnation of the decayed and the fouled. (5).Insufficient defensive and nutrition qi, meridians stagnated by coldHuangQi.GuiZhi WuWuTang is used in the syndrome of both deficient nutrition qi and defensive qi, wind cold attacking meridians and blood vessel stasis; DangGui SiNiTang is used in the syndrome of insufficient nutrition blood, cold stagnation in meridians and both hand foot coldness. (6).Cold exteriorly and interiorly, disharmony between nutrition qi and defensive qi; prolonged wind dampness, bi syndrome affecting both nutrition qi and defensive qiGuiZhiTang with WuTou is used in the syndrome of exuberant yin with declined yang, internal obstructed cold qi, unsmooth qi activity, exterior cold evil and disharmony between nutrition qi and defensive qi; GuiZhi ShaoYao ZhiMuTang is used in the syndrome of upper attaching, middle obstruction, lower flow of wind evil, wind dampness penetrating deeply into joints .tendons and bones, stagnation of yang qi, unsmooth qi and blood and bi syndrome due to both impairment of nutrition qi and defensive qi. (7).Insufficient qi and blood, deficient yin and yangXiaoJianZhongTang is used in the syndrome of deficient diarrhea and cold heat miscellaneous disease due to insufficient spleen nutrition qi, disharmony between yin and yang, and between qi and blood; ZhiGanCaoTang is used in the syndrome of palpation and obstructed pulse due to deficient heart yin and heart yang; ShaoYaoGanCaoTang is used in the syndrome of deficient yin and yang, blood and humoral insufficiency, malnutrition tendons and vessels. (8).Disharmony between nutrition qi and defensive qi, disharmony between water and qiAt the time disharmony between nutrition qi and defensive qi(qi and blood) occurs, yin qi and yang qi fails to flow and syndrome of disharmony between qi and water takes place: GuiZhiTang with FuLing, BaiChu, getting rid of GuiZhi is used in the syndrome of exterior disharmony between nutrition qi and defensive qi with internal disharmony between water and qi; HuangQi ShaoYao GuiZhi KuJiuTang is used in the yellow sweating syndrome of nutrition qi and defensive qi stagnation,water dampness invasion, yang depressed due to dampness stagnation; GuiZhiTang with HuangQi is used in the yellow sweating syndrome of disharmony between nutrition qi and defensive qi and dampness invasion due to deficient defensive qi; GuiZhiTang with MaHuang, XiXin, FuZi, getting rid of ShaoYao is used in the syndrome of yang deficiency while yin stagnation, unsmooth nutrition qi and defensive qi and stagnation of qi and water.V.a Survey of Theoretical, Clinical and Experimental Research of Syndrome Differentiation GuiZhiTang (Omit)Part 2 Laboratory ResearchPurpose: Influence of GuiZhi Tang to humoral immunity of rats in the case of deficient spleen syndrome. (IGG, IGM, alexin C3); researching the modulation of active NF-ATc to Th-Cell differetion of deficient spleen rats in the cytoimmunity and the interference of GuiZhiTang.Method: Construction of spleen deficiency rats by improving spleen deficiency rats mold. 40 SD rats (4 group): Common group (Group A), Spleen Deficiency Mold group ( Group B), GuiZhi Tang Heavy Dose group(Group C), GuiZhi Tang Light Dose group(Group D). Using Diffraction Filtration Erosion to test IGG IGM and alexin C3 in the serum of rats, using PCR test the expression of NF-ATc, IL-4, IFN-y mRNA and interfering of GuiZhi Tang to IgG, IgM, alexin C3, NF-ATc, IL-4, IFN-ymRNA. Results: expression of NF-ATc mRNA and IL-4mRNA were accelarated, rFN-ymRNA was declined in Spleen Deficiency Mold group ( Group B), expresion of NF-ATc x EL-4 mRNA were declined, expression of IFN-y mRNA was accelarated in GuiZhi Tang Heavy Dose group(Group C) and GuiZhi Tang Light Dose group(Group D).ResuIts: In humoral immunology, compared to group A, IgGIgM component in rats serum of group B declined obviously(P<0.01) while alexin C3 ascended obviously(P>0.05), IGG andIGM in rats serum of group C and Group D ascended obviously more than group B(P<0.05) while alexin C3 declined obviously.In cytoimmunity, compared to group A, NF-ATcmRNA, IL-4 mRNA of group B ascended obviously(P<0.05) while IFN-y mRNA expression declined obviously(P<0.05); after heavy dose and light dose application of GuiZhiTang, NF-ATc mRNA> IL-4 mRNA expression of group C and group D declined (P<0.05) , IFN-y mRNA expression ascended (PO.05). Compared to group A, there index acquired normal level basically.Cone I us i on: In humoral immunity test, GuiZhi Tang Heavy Dose group and GuiZhi Tang Light Dose group produced good regulation to IGG and IGM in rats serum, that is, GuiZhi Tang increases IGG and IGM in rats serum. Possible explanation of GuiZhi Tang in strenghthenning humoral immunity of rats is that GuiZhi Tang invigorated spleen and stomach to increase the formation and excretion of IGG and IGM, and further to improve humoral immunity. Alexin C3 in

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