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大黄黄连泻心汤、理中丸对消炎痛型胃溃疡寒热证模型大鼠的影响及其方证相应性研究
The Influence of Dahuang Huanglian Xiexin Decoction and Lizhong Pill on the Gastric Ulcer Model Induced by Indomethacin in the Cold or Heat Syndrome Rats and the Rules of Recipe Corresponding to Syndrome
【作者】 于海；
【导师】 李冀；
【作者基本信息】 黑龙江中医药大学 ， 方剂学， 2010， 博士
【摘要】 建立消炎痛型胃溃疡中医寒热证模型,并初步探讨其形成机制和相应寒热方剂大黄黄连泻心汤、理中丸对消炎痛型胃溃疡寒热证模型的部分作用机理及其方证相应规律,以及寒热模型间的微观差异性。方法采用寒（冰水+0.3mol/L氢氧化钠）、热（辣椒+60﹪乙醇）因素与消炎痛腹腔注射结合的方法,分别建立大鼠胃溃疡病证结合的寒、热证模型,再选用寒热不同性质的方剂（大黄黄连泻心汤、理中丸）对其进行交叉治疗,并检测各模型组和治疗组大鼠SOD、MDA、VEGF、bFGF、IL-8、TNF-α、HGE2、TXB2、NT、GAS等指标的变化情况。结果1、各造模因素可不同程度的通过增加IL-8和TNF-α的表达、提高Gas含量、加速TXB2的释放,升高MDA含量,降低SOD活力,减少PGE2的合成和释放,抑制NT的分泌,加速对胃黏膜的破坏,促进溃疡的形成,并可代偿性的提高VEGF、bFGF含量,以促进机体修复胃黏膜损伤。2、热性方剂理中丸对寒性模型、寒性方剂大黄黄连泻心汤对热性模型都产生了较好的治疗效果,体现了有选择性的证治效应。推测其可能是通过提高大鼠SOD活性,降低MDA含量,刺激胃黏膜,提高对VEGF、bFGF的释放,抑制炎性因子IL-8、TNF-α产生,降低Gas、TXB2合成,抑制Gas分泌,提高NT和PGE2的释放,来修复受损的胃黏膜。3、各造模因素在增加IL-8、TNF-α表达和升高MDA、Gas含量的程度方面,以热性模型组更为显著;而在增加TXB2释放的程度方面,则以寒性模型组更为显著。结论在“方证相应”理论指导下,通过“以方测证”的方法,验证了本实验所采用的“病证结合”的消炎痛型胃溃疡寒热模型复制成功,并探讨了消炎痛型胃溃疡寒热证形成的部分机制及寒热模型间的部分微观差异性。
【Abstract】 ObjectTo establishing the model of gastric ulcer induced by indomethacin combined with cold or heat syndrome, and to exploring its forming mechanism,the partial mechanism of action of dahuang huanglian xiexin decoction and lizhong pill and the rules of recipe corresponding to syndrome. MethodAdopting cold factor （ice water +0.3mol/LNaOH）、heat factor（capsicum+ 60﹪ethanol） combined with indomethacin intraperitoneal injection, to establish the model of gastric ulcer combined with cold or heat syndrome , which is the model of“disease combined with syndrome”.Then selecting two contradictory nature prescriptions（Dahuang huanglian xiexin Decoction、Lizhong Pill）to cross-fire treatment. Detecting the indexes of every groups, SOD、MDA、VEGF、bFGF、IL-8、TNF-α、PGE2、TXB2、NT、GAS.Results1、Each making-model factor can accelerate the destruction of gaster-mucosa, promoting the formation of ulcer at different degrees through increasing the expression of IL-8 and TNF-α, increasing the contents of Gas and MDA, accelerating the release of TXB2, decreasing the energy of SOD and the synthesis- release of PGE2, inhibiting the secretion of NT. Simultaneously, each factor also can increase the contents of VEGF、bFGF,to promote the recovery of gaster-mucosa damage.2、Heat nature prescription Lizhong Pill produce a marked effect to cold mode, and cold nature prescription Dahuang huanglian xiexin Decoction produce a conspicuous effect to heat model, which indicate the selectional syndrome-treatment potency. The two prescriptions can recover the gaster-mucosa damage of corresponding model through increasing the energy of SOD, decreasing the contents of MDA, increasing the release of VEGF、bFGF, inhibiting the generation of inflammatory factors IL-8、TGF-α, decreasing the synthesis of Gas、TXB2, inhibiting the secretion of Gas, increasing the release of NT、PGE2。 3、The degrees of increasing the expression of IL-8 and TNF-α, and of increasing the contents of MDA and Gas indicate more strikingly in heat models. The degree of increasing the release of TXB2 manifests more obviously in cold models. ConclusionOn the basis of the theory of“prescription-syndrome corresponding”, through the method of“infering syndrome by prescription”verifying the success of duplicating“disease-syndrome combination model”, that is the model of gastric ulcer induced by indomethacin combined with cold or heat syndrome. Elucidating the partial forming mechanism of this model, and the microcosmic variability between cold model and heat model.