【作者】 柴剑波；

【导师】 李冀；

【作者基本信息】 黑龙江中医药大学 ， 方剂学， 2009， 博士

【摘要】 目的建立幽门结扎型胃溃疡寒热证动物模型，探究其证侯变化规律及物质基础，阐明寒热方剂(大黄黄连泻心汤、理中丸)的作用机制及方证相应规律，为临床辨治溃疡病提供实验依据。同时，为以“病证结合”模式之中医证型研究提供方法学新途径。方法及内容采用经典幽门结扎法复制大鼠胃溃疡模型，同时施加“寒热”因素(冰水、0．3 mol／LNaOH，8％干辣椒粉的60％乙醇混悬液)创建幽门结扎型胃溃疡寒热证病证结合动物模型，观察寒热方剂大黄黄连泻心汤、理中丸对所创建模型的方证相关性影响。幽门结扎术后18h处死各模型及给药组大鼠，测定各模型及给药组大鼠溃疡指数及血清中肿瘤坏死因子(TNF-a)、白介素-8(IL-8)、内皮素(ET)、一氧化氮(NO)、一氧化氮合酶(NOS)含量；胃组织匀浆检测表皮生长因子(EGF)、转化生长因子(TGF-a)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量；脑组织匀浆检测5-羟色胺(5-HT)、去甲肾上腺素(NE)含量。结果(1)幽门结扎型胃溃疡热证：SOD活力降低，MDA、NO、iNOS含量升高，IL-8、INF-α表达量增加，Gas含量升高，EGF、TGF-a含量降低，NE、5-HT含量升高。大黄黄连泻心汤能提高其SOD活性，降低MDA含量，抑制炎性因子IL-8、TNF-a产生，减少NO及NOS合成，刺激胃黏膜EGF、TGF-a释放，降低NE、5-HT合成，抑制Gas分泌。其防治作用的机制可能主要与增强抗氧化能力、抑制炎症反应、调节胃肠激素、刺激生长因子释放及调整中枢神经系统有关。(2)幽门结扎型胃溃疡寒证：SOD活力降低，MDA含量升高，NO、TNOS含量降低，ET含量升高，NO／ET比值降低，TNF-α表达量增加，Gas含量升高，EGF、TGF-a含量降低，5-HT含量升高。理中丸可提高其SOD活性，降低MDA含量，提高NO含量，降低ET含量，协调NO／ET比例关系，刺激胃黏膜EGF、TGF-α释放，抑制Gas分泌，降低TNF-a含量，提高交感-肾上腺髓质机能活动而降低5-HT含量。其防治作用的机制可能主要与增强抗氧化能力、调节胃肠激素、增强胃黏膜血流、抑制炎症反应、刺激生长因子释放及调整中枢神经系统有关。结论(1)采用“寒热因素”(冰水、0．3mol／LNaOH，8％干辣椒粉的60％乙醇混悬液)结合幽门结扎法可成功建立幽门结扎型胃溃疡寒热证动物模型。(2)幽门结扎型胃溃疡寒热证在抗氧化能力、胃黏膜血流、炎症因子、胃泌素、神经递质、生长因子等“微观辨证”方面具有一定的差异性。(3)大黄黄连泻心汤、理中丸在寒热病证结合模型上体现了不同的证治效应，对相应的寒热证模型有选择性，体现了相应方治疗相应证的证治规律，是一种方证相应的实验结果。本研究可为中医证型本质研究提供方法学参考，为中医理论的进一步发展奠定理论及实验基础。更多还原

【Abstract】 Objective of the researchFound pyloric ligature model of cold and pyretic syndrome ulcer whichhas the fortes of easy operability,good constancy and repeatabilty,drawassistance from the model to reveal the essence and material foundation ofGastric ulcer of cold and pyretic syndrome though the observation on rules ofcold and pyretic syndrome of Gastric ulcer,research function mechanisms andmaterial foundation of cold or heat formulas(Dahuang Huanglian XiexinDecoction、Lizhong Pill) and rules of recipe corresponding of syndrome,offer the rationale basis and experimental evidence for pathogenesis obtainedthrough differentiation of symptoms and signs in the traditional Chinesemedicine clinic and provide the study on traditional Chinese medicinesyndromes in the mode of combination of diseases with syndrome with thereference in the technology.It has an important sense for the diagnose,pathogenesis obtained through differentiation of symptoms and signs,treatment and study on normalization of pathogenesis obtained throughdifferentiation of symptoms and signs in the traditional Chinese medicineclinic.Method and content of the researchBased on academic thought of professor Li Ji’s recipe corresponding tosyndrome and results of the peptic ulcer and literature research from his team,regard pathogenesis of cold or pyretic syndrome obtained throughdifferentiation of symptoms and signs in traditional Chinese medicine as theprinciple.Found pyloric ligature model of cold and pyretic syndrome ulcerbased on the traditional chines medicine theory of etiological factor andpathogenesis and modern medicine methods by means of authenticatingcontradistinction of recipe corresponding to syndrome and means ofduplicating pyloric ligature Gastric ulcer model of rats and exerting cold andheat factors(mixed liquor of ice water +0.3 mol/ml NaOH or 8% dry paprica+60% alcohol) on the model rats.Observe the effect of cold formula Dahuang Huanglian Xiexin Decoction and heat formula Lizhong Pill on the foundedmodel at the recipe corresponding to syndrome.Killed the rats seven hoursafter water-stress.Detected the ulcer index,the content of TNF-a,IL-8,ET,NO and INOS in blood serum.Detected the EGF,TGF-a,SOD andMDAin the stomach tissue.Detected the content of 5-HT and NE in the brain tissue.Results(1) In the pyloric ligature model of pyretic syndrome,SOD,EGF andTGF decrease,MDA,NO,iNOS,IL-8 and INF-αexpression,Gas and NE stepup.Dahuang Huanglian Xiexin Decoction can raise SOD,decrease MDA,irritate the Gastric mucosa to release EGF and TGF-α,restrain IL-8,TNF-αand GAS and decrease sympathesis-adrenal medulla function to make thecontent of NE down.Its function mechanism against Gastric ulcer may beconcerned with releasing the damage to Gastric mucosa by means ofrestraining the lipid peroxidation from free radical in the body,inflammationreaction and Gas secretion,with enhancing the defensive capability in theGastric mucosa and with adjusting the function of central nervous system.(2) In the pyloric ligature model of cold syndrome,SOD,NO,TNOS,NO/ET,EGF and TGF decrease,MDA,ET,TNF-αexpression,Gas and 5-HTstep up.Lizhong Pill can raise SOD and NO,decrease MDA and NT,adjustET/NO,irritate the Gastric mucosa to release EGF and TGF-α,elevatesympathesis-adrenal medulla function to make the content of 5-HT down andrestrain Gastrin.Its function mechanism against Gastric ulcer may beconcerned with releasing the damage to Gastric mucosa by means ofrestraining the lipid peroxidation from free radical and GAS secretion,withenhancing the defensive capability and blood current in the Gastric mucosaand with adjusting the function of central nervous system.Conclusion(1) In the pathology cold and heat formulas can ameliorate or preventand cure the changes of pyloric ligature animal model of cold and pyreticsyndrome Gastric ulcer which is founded by means of combining pyloricligature with cold and heat factors.This is an experimental result of recipe corresponding to syndrome and indicates that this method to found Gastriculcer of cold and heat syndrome is successful.(2) There are differents between heat syndrome and cold syndrome ofpyloric ligature Gastric ulcer in the diversity of indexes including semeiology,anti-oxidation capability,blood current in the Gastric mucosa,inflammatory factor,neurotransmitter,gut hormone and growth factor,revealthe essence micro-indications.(3) Dahuang Huanglian Xiexin Decoction、Lizhong Pill can aim directlyat the pyloric ligature Gastric ulcer of cold or heat syndrome.That is a resultof Recipe Corresponding to Syndrome.This research can offer the reference in technology for the study on theessence of combining disease with syndrome and establish the foundation oftheory and experiment for the further development of traditional Chinesemedicine.更多还原