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水浸应激型胃溃疡寒热证模型的建立与相关性方剂对其影响的研究

发布时间:2018-11-21 11:01
【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。
[Abstract]:Objective: to explore the mechanism of stress ulcer cold and heat syndrome and reveal the essence of stress ulcer cold and heat syndrome by combining the water-immersion stress gastric ulcer disease model with traditional Chinese medicine cold and heat syndrome. To observe the action mechanism and the corresponding law of formula of rhubarb, Huanglian Xiexin decoction and Lizhong Pill on stress type ulcer model of cold and heat syndromes, and to observe the effect of rhubarb and Huanglian Xiexin decoction on the model of stress ulcer and heat syndrome. Methods: cold factors (ice water, 0.3mol/L sodium hydroxide) and heat factors (8% capsicum powder, 60% ethanol) were used to establish gastric cold and gastric heat syndrome model. Heat syndrome combined model, cold formula rhubarb, Huanglian Xiexin decoction, heat prescription Lizhong pills were treated by gastric perfusion. 1. After 7 hours of restraint water immersion stress, the rats of each model and drug group were killed. The ulcer index and serum levels of tumor necrosis factor (TNF-a), interleukin-8 (IL-8), endothelin (ET),) nitric oxide (NO), synthase (INOS) were measured in each model and administration group. 2. The contents of epidermal growth factor (EGF), transforming growth factor (TGF-a) and superoxide dismutase (SOD),) malondialdehyde (MDA) were detected in gastric homogenate. 3. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were measured in brain homogenate. Results: 1, the ulcer index of cold water group, hot water group and single water group were significantly higher than that of single water group (P < 0.01). Compared with cold water group and hot water group, cold water and hot water decreased significantly (P < 0. 01). 2. In SOD,EGF and TGF-a, cold water and hot water decreased in different degrees compared with blank group (P < 0. 01). The content of TGF-a in hot water group was lower than that in cold water group (P < 0. 01). The contents of cold water, hot water and hot water were significantly higher than those of hot water (P < 0. 01 or P < 0. 05). 3. In MDA,NO,INOS,IL-8,TNF-a and NE, hot water was compared with blank and cold water group. The content increased (P < 0.01 or P < 0.05). After treatment with rhubarb Huanglian Xiexin decoction, the content of hot water was lower than that of hot water (P < 0. 05 or P < 0. 01). 4. In ET,5-HT, compared with blank and hot water group, the content of rhubarb in cold water group was significantly higher than that in hot water group (P < 0. 01). Compared with cold water, the content of cold water decreased significantly (P < 0.01). Conclusion: 1. The pathogenesis of water-immersion stress type ulcers is not only related to the overall factors such as neuroendocrine disorders, but also to local factors such as weakened gastric mucosal protection and increased injury factors. 2, the heat syndrome of water-immersion stress ulcer was related to the decrease of the content of superoxide dismutase (SOD), epidermal growth factor (EGF), transforming growth factor (TGF-a); It was associated with the increase of (INOS), tumor necrosis factor (TNF-a), interleukin-8 (IL-8) and norepinephrine (NE) in malondialdehyde (MDA), nitric oxide (NO),) nitric oxide synthase (INOS),). 3. The cold syndrome of water-immersion stress ulcer was related to the decrease of the content of superoxide dismutase (SOD), nitric oxide (NO), epidermal growth factor (EGF), transforming growth factor (TGF-a). Endothelin 5-hydroxytryptamine (5-HT) is associated with an increase in endothelin 5-hydroxytryptamine (5-HT) content. 4. The mechanism of rhubarb Huanglian Xiexin decoction in preventing heat syndrome of water-immersion stress ulcer may be related to increasing SOD activity, decreasing MDA content, reducing inflammatory reaction of NO,INO S and stimulating EGF,TGF-a release from gastric mucosa. Inhibition of inflammatory factor IL-8,TNF-a and decrease of sympathetic-adrenomedullary activity and decrease of NE content. 5. The mechanism of Lizhong Pill in preventing cold syndrome of water-immersion stress ulcer may be related to increasing SOD activity, increasing NO content, decreasing ET content, improving gastric mucosal blood flow and stimulating gastric mucosal EGF,TGF-a release. Increased sympathetic-adrenomedullary activity and decreased 5-HT content.
【学位授予单位】:黑龙江中医药大学
【学位级别】:博士
【学位授予年份】:2009
【分类号】:R-332;R285

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