【作者】 毕珺辉；

【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：将水浸应激型胃溃疡疾病模型与中医寒、热证相结合，探讨应激型溃疡寒、热证形成机制，揭示应激型溃疡寒、热证候实质；观察寒性方剂大黄黄连泻心汤、热性方剂理中丸对应激型溃疡寒、热证模型的作用机理及方证相应规律。方法：采用寒因素(冰水、0．3mol／L氢氧化钠)及热因素(8％辣椒粉、60％乙醇)建立胃寒、胃热证模型，结合国内外较为公认的束缚水浸应激法创建应激型溃疡寒、热证结合模型，寒性方剂大黄黄连泻心汤、热性方剂理中丸灌胃治疗。1、束缚水浸应激7h后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(INOS)含量；2、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；3、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、在溃疡指数方面，寒水组、热水组与单水组比，明显升高(P＜0．01)；寒水理、热水大分别与寒水、热水组比，明显降低(P＜0．01)。2、在SOD、EGF及TGF-a方面，寒水、热水与空白组比较，均有不同程度的下降(P＜0．01)，热水组TGF-a含量低于寒水组(P＜0．01)；寒水理与寒水、热水大与热水比较，含量均明显升高(P＜0．01或P＜0．05)。3、在MDA、NO、INOS、IL-8、TNF-a及NE方面，热水与空白、寒水组比较，含量升高(P＜0．01或P＜0．05)；大黄黄连泻心汤治疗后，热水大与热水比较，含量降低(P＜0．05或P＜0．01)。4、在ET、5-HT方面，寒水组与空白、热水组比较，升高明显(P＜0．01)；理中丸治疗后，寒水理与寒水比较，含量明显降低(P＜0．01)。结论：1、水浸应激型溃疡寒、热证的发病机制既与整体因素如神经-内分泌失调有关，又与局部因素如胃黏膜保护功能减弱和损伤因素增强有关。2、水浸应激型溃疡热证与超氧化物歧化酶(SOD)、表皮生长因子(EGF)、转化生长因子(TGF-a)含量降低有关；与丙二醛(MDA)、一氧化氮(NO)、一氧化氮合酶(INOS)、肿瘤坏死因子(TNF-a)、白介素-8(IL-8)、去甲肾上腺素(NE)含量升高有关。3、水浸应激型溃疡寒证与超氧化物歧化酶(SOD)、一氧化氮(NO)、表皮生长因子(EGF)、转化生长因子(TGF-a)含量降低有关；与内皮素(ET)、5-羟色胺(5-HT)含量升高有关。4、寒性方剂大黄黄连泻心汤预防水浸应激型溃疡热证的作用机制可能与提高SOD活性、降低MDA含量、减少NO、INO S的炎性反应、刺激胃黏膜EGF、TGF-a释放、抑制炎性因子IL-8、TNF-a产生、降低交感-肾上腺髓质机能活动而减少NE含量有关。5、热性方剂理中丸预防水浸应激型溃疡寒证的作用机制可能与提高SOD活性、提高NO含量、降低ET含量而改善胃黏膜血流量、刺激胃黏膜EGF、TGF-a释放、提高交感-肾上腺髓质机能活动而降低5-HT含量有关。更多还原

【Abstract】 Object:To establish evaluation criterion of the models of stress-restrainulcer with cold and hot syndrome.Reveal the essential of stress-restrain ulcermodels with cold and hot syndrome.Observe the mechanism,material basisand regulation of formula-symptom corresponding of Dahuang HuanglianXiexin Decoction and Lizhong Pill on the models of stress-restrain ulcer withcold and hot syndrome.Methods:Use cold factor(cold water,0.3mol/L NaOH)and hot factor(8%pepper powder,60% ethanol mixed solution)to establish the model of coldand hot syndrome combined with water immersion stress method which hasbeen received by domestic and abroad scholar,and treat with DahuangHuanglian Xiexin Decoction of cold property and Lizhong Pill of hot property.1.Killed the rats seven hours after water-stress.Detected the ulcer index,thecontent of TNF-a,IL-8,ET,NO and INOS in blood serum.2.Detected theEGF,TGF-a,SOD and MDA in the stomach tissue.3.Detected the content of5-HT and NE in the brain tissue.Results:1.In ulcer index aspect,compared to the water-stress group,theulcer index of the cold syndrome with water-stress group and the hotsyndrome with water-stress group were increased apparently(P＜0.01)Theindex of the cold syndrome with water-stress group treated with Lizhong Pilland the hot syndrome with water-stress group treated with DahuangHuanglian Xiexin Decoction were decreased apparently compared to the coldsyndrome with water-stress group and the hot syndrome with water-stressgroup respectively(P＜0.01)2.Compared to the blank group,the content ofSOD.EGF and TGF-a of the cold syndrome with water-stress group and thehot syndrome with water-stress group decreased(P＜0.01).The content ofTGF-a decreased in the hot syndrome with water-stress group(P＜0.01)compared to the cold syndrome with water-stress group.The content of thecold syndrome with water-stress group treated with Lizhong Pill and the hotsyndrome with water-stress group treated with Dahuang Huanglian XiexinDecoction were increased apparently compared to the cold syndrome with water-stress group and the hot syndrome with water-stress group respectively(P＜0.01 or P＜0.05)3.Compared to the blank group and the cold syndromewith water-stress group,the contents of MDA.NO.INOS.IL-8.TNF-a andNE increased in the hot syndrome with water-stress group(P＜0.01 or P＜0.05).Compared to the hot syndrome with water-stress group,the contents of MDA.NO.INOS.IL-8.TNF-a and NE decreased in the hot syndrome withwater-stress group treated with Dahuang Huanglian Xiexin Decoction(P＜0.01or P＜0.05).4.Compared to the blank group and the hot syndrome withwater-stress group,the contents of 5-HT and ET increased in the coldsyndrome with water-stress group(P＜0.01 or P＜0.05)After treated byLizhong Pill,compared to the cold syndrome with water-stress group,thecontents of 5-HT and ET decreased in the cold syndrome with water-stressgroup(P＜0.01)Conclusions:1.The mechanism of cold syndrome and hot syndrome with water stresshave relationship with general factor such as nerve-endocrine and local factorsuch as protection function and damage function of gastric mucosa.2.Hot syndrome with water stress ulcer model has relationship with thedecreasing of SOD,EGF and TGF-a,and has relationship with the increasingof MDA,NO,INOS,TNF-a,IL-8 and NE.All these can be seen asmicro-indications for clinical acute ulcer with hot syndrome.3.Cold syndrome with water stress ulcer model has relationship with thedecreasing of SOD,NO,EGF and TGF-a and has relationship with theincreasing of 5-HT and ET.All these can be seen as micro-indications forclinical acute ulcer with cold syndrome.4.The mechanism of the cold formulae,Dahuang Huanglian XiexinDecoction,to prevent the water-stress induced ulcer with hot syndrome hasrelationship with increasing the activity of SOD,decreasing the content ofMDA,reducing the inflammatory reaction of NO.INOS,stimulating thereleasing of EGF、TGF-a,inhibiting the releasing of IL-8 and TNF-a anddecreasing the activity of sympathetic adrenal and content of NE.5 The mechanism of the hot formulae,Lizhong Pill,to prevent the water-stress induced ulcer with cold syndrome has relationship withincreasing the activity of SOD,increasing the content of NO,decreasing thecontent of ET and mproving the gastric mucosal blood flow.stimulating thereleasing of EGF、TGF-a.Increasing the activity of sympathetic adrenal anddegrading content of 5-HT.更多还原