清热解毒、消痈生肌法对乙酸致胃溃疡大鼠溃疡愈合影响的实验研究

【作者】 肖景东；

【导师】 周学文；

【作者基本信息】 辽宁中医药大学 ， 中医内科学， 2008， 博士

【摘要】 消化性溃疡是临床中的常见病和多发病,具有病程长、反复发作、表现复杂等特点。现代医学对消化性溃疡的病因及发生机制尚未完全阐明。目前西医采用根除幽门螺杆菌和制酸治疗虽可取的较好疗效,但部分疣状病灶常持续存在,不易消退。用常规抗酸治疗的溃疡,停药后一年复发率可高达60%。导师周学文教授根据消化性溃疡的临床症状及胃镜下的形态学特征,创立“毒热”病因学说。本课题旨在研究、探讨基于“清热解毒、消腐生肌”之法拟成“消痈溃得康”煎剂的药效及作用机制,从多角度揭示中医药治疗胃溃疡的机理,并从理论上阐述“毒热”病机,以及“以痈论治”消化性溃疡的学术思想。研究目的:运用免疫组织化学染色和计算机图像分析仪技术半定量评价中药消痈溃得康煎剂治疗乙酸致胃溃疡大鼠胃溃疡的愈合效果,并且利用分子生物学技术,从生长因子和三叶因子角度探讨该方治疗胃溃疡的作用机理,进一步揭示“毒热”病因,以及“以痈论治”消化性溃疡的学术思想。材料与方法:1.制作乙酸致胃溃疡大鼠模型,随机分为6组,分别为:正常组、模型组、中药治疗组、中药低剂量治疗组、中成药治疗组、西药治疗组。2.按研究方案对实验对象进行药物研究治疗。3.治疗结束后进行常规理化检验,包括测量大鼠胃液排出量、胃液酸度、溃疡面积等,以及对溃疡组织进行病理染色切片的形态学观察。4.计算溃疡指数、溃疡抑制率,评价溃疡的愈合质量。5.采用放射免疫分析方法,通过测定表皮生长因子(EGF)含量及其受体EGFR的表达评价治疗效果。6.利用分子生物学技术,通过测定三叶因子(TFF2)表达情况评价治疗效果。结果:1.消痈溃得康煎剂能实现对大鼠胃溃疡愈合因素的影响,减少胃液分泌、降低胃液酸度,减轻攻击因素对胃粘膜的侵害,减少溃疡面积,促进溃疡的愈合,并具有相应的量效关系。2.消痈溃得康煎剂能促进溃疡部位肉芽组织形成,使溃疡再生粘膜厚度明显升高,提高溃疡抑制率,显著降低溃疡指数,并具有相应的量效关系。3.消痈溃得康煎剂能提高大鼠胃溃疡组织EGF含量,增加EGFR在溃疡粘膜的表达,提高粘膜再生修复能力,加速溃疡的愈合。4.消痈溃得康煎剂能提高大鼠胃溃疡组织TFF2的表达,提高粘膜再生修复能力,加速溃疡的愈合。结论:“清热解毒、消痈生肌”治法对乙酸致胃溃疡大鼠治疗是有效的,“毒热”病因在胃溃疡的发病中是客观存在的。更多还原

【Abstract】 Gastric ulcer(GU) is one of the common diseases in clinics, processing the characteristics of long course, recurrence, complex performance. The etiology and mechanism of onset of GU have not been fully clarified yet in modern medicine. The treatment of dradication of helicobacter pylori and anti-acid can get good efficacy, but partful verrucous lesions often persist and do not dissipate.The recurrence rate of the ulcer conventionally treated with anti-acid one year after the withdrawal can be as high as 60%. Professor Zhou Xuewen create the etiological theory of toxin-heat, according to the clinical manesfestations and the morphological features of gastroscope of GU. The research work is to discuss the efficacy and pharmacodynamics mechanism of the decoction Xiaoyongkuidekang(XYKDK) composed according the theoraputic method of clearing away the heat while detoxifying the body, and elimianting the carbuncle while growing muscle, so as to discuss the mechanism of treating gastric ulcer with TCM. The pathogenisis of toxin-heat and theoraputic thinking of treating peptic ulcer as carbuncle are theoretically expounded.ObjectsThis study estimated the acetic acid-induced gastric ulcer in rats treated with XYKDK by immunohistochemical staining and computer image analysis quantitative assessment.It also investigated the possible therapeutic mechanisms of XYKDK treating gastric ulcer from the aspect of growth factor and trefoil factor, so as to further explain the eitology of toxin-heat and the acdemical thinking of treating peptic ulcer as carbuncleMethods1. The rat model of acetic acid-induced gastric ulcer was established. And the rats were devided into six groups: blank control, GU model, Weikang capsule, Cimetidine, XYKDKⅠ(small dose) and XYKDKⅡ(1arge dose)groups.2. To treat the rat model according to the research plan.3. The normal tests were conducted after treatment, including measurement of gastric juice, gastric acidity, ulcers area, as well as the observation of stained sections of ulcer tissue.4. Gastric ulcer index and gastric ulcer inhibition ratio were measured, and the condition of ulcer healing was evaluated.5. The content of epidermal growth factor (EGF) and the expression of its receptor(EGFR) were measured to evaluate the efficacy by the radioimmunoassay method.6. The expression of trefoil factor(TFF)was determined by molecular biology techniques.Results:1. XYKDK has effecet on healing factors of gastric ulcer in rats, reducing gastric juice, gastric acidity, the damage of the gastric mucosa and ulcers area, and promoting healing of the ulcer, which have Dose-effect relationship.2. XYKDK promotes the formation of ulcer granulation tissue, increasing regenerated mucosa thickness, reducing the ulcer index significantly, which have Dose-effect relationship.3. XYKDK improves the EGF concentration in rat gastric ulcer tissue, increasing the EGFR expression in mucosal ulceration, enhancing regeneration and repair capability of mucosa, so as to accelerate ulcer healing.4. XYKDK increases the expression of TFF in rat gastric ulcer tissue, enhancing regeneration and repair capability of mucosa, so as to accelerate ulcer healing.Conclusion:The theorapetic method of clearing away the heat while detoxifying the body, and elimianting the carbuncle while growing muscle is effictive, and the etiology of toxin-heat do exist during the onset of gastric ulcer.更多还原