【作者】 李丹；

【导师】 唐方；

【作者基本信息】 天津医科大学 ， 中西医结合临床， 2009， 硕士

【摘要】 目的肠易激综合征(Irritable bowel syndrome, IBS)是一种以腹部不适或腹痛、排便习惯和大便性状异常为主要症状而又缺乏胃肠道结构或生化异常的胃肠功能性疾病。研究发现造成IBS的因素是多方面的,以感觉异常和动力改变为特征的内脏高敏感性是其主要发病机制之一。目前认为神经-免疫-内分泌网络失调是对IBS较为全面的认识,胃肠激素、免疫因子作为该网络的中间递质在IBS发病机制中发挥着重要作用。IBS发病广泛,西医治疗以对症处理为主,而无有效的根治措施,中医中药治疗取得了满意的临床疗效,具有广阔的应用前景。腹泻型肠易激综合征(D-IBS)归属于中医“泄泻”、“腹痛”等范畴,多种致病因素均能影响脾胃升清降浊功能,导致小肠泌清别浊失调,水谷并走肠间,引发泄泻。’芳香运脾类方药,具有补中寓消,消中有补,补不碍滞,消不伤正之功。既能消除阻碍脾胃正常纳运的各种致病因子,以及因脾胃纳运失常而产生的各种病理产物如湿、食、滞等；又能促进脾胃机能的恢复,使之达到健运的正常状态。其代表方药藿香正气具有疏畅中焦气机,宣化湿浊,运脾醒胃之功效,对湿邪停滞,脾胃不和所致外感及内伤腹泻具有明确的临床止泻作用,其双向调整胃肠动力,保护肠屏障,调畅心神的功能,提示本类方药可能成为治疗D-IBS的理想药物。本研究以腹泻型肠易激综合征(D-IBS)为重点,通过观察藿香正气方药对D-IBS大鼠胃肠激素和免疫炎症因子的调节作用,试图阐释芳香运脾方药对于D-IBS内脏敏感性和免疫炎症失衡的调整作用以及相关的药理机制,并为临床应用该类药物治疗D-IBS提供科学翔实的实验依据。方法1.以番泻叶灌胃联合肢体束缚应激法复制腹泻型肠易激综合征大鼠模型。2.通过观察不同浓度藿香正气对模型大鼠大体指标、甩尾时间、直结肠球囊扩张耐受阈值的影响,初步探讨藿香正气对D-IBS大鼠模型敏感性的影响,并确定最佳使用浓度。3.通过对结肠粘膜匀浆SP、VIP、CGRP、血浆ET含量的测定,探讨藿香正气对相关敏感性胃肠激素的影响。4.通过测定血浆ET、结肠粘膜匀浆SP、VIP的水平,探讨藿香正气主药藿香水提液、挥发油、以及水油混合成分,对相关胃肠激素的影响。5.通过脏体指数、血清及结肠粘膜中IL-1β、IL-2浓度、血清CORT的测定,探讨藿香正气对炎症免疫失衡的调节作用。结果1.成功改良并复制D-IBS动物模型。模型组大鼠均腹泻,体重呈负增长(P<0.01),免疫器官萎缩(P<0.01)。光镜下结肠组织病理学表现为局部上皮细胞排列不整,杯状细胞增多,粘膜下偶有水肿,间质少许炎性细胞浸润。2.芳香运脾代表方-藿香正气高、中剂量组不但可以明显抑制模型大鼠体重下降(P<0.01),减少稀便(P<0.05),而且能够明显改善其躯体及肠道敏感性的异常状态(P<0.05),尤以中浓度组(53.6mg/ml)作用最为显著。3.芳香运脾代表方-藿香正气可显著降低外周SP、VIP、ET水平(P<0.01,P<0.05,P<0.01),维持CGRP含量(P>0.05)。4.芳香运脾代表药-藿香可显著降低外周SP、VIP及ET含量(P<0.01),藿香水提液、挥发油作用靶点不同。5.芳香运脾代表方-藿香正气可提高脏体指数(P<0.05),有效降低IL-1B水平(P<0.05),明显提高IL-2含量(P<0.01),发挥免疫调节作用,但对于CORT含量无明显降低作用(P>0.05),。结论本研究以番泻叶水煎剂灌胃联合肢体束缚应激法,成功改良并复制了腹泻型肠易激综合征大鼠模型。芳香运脾法代表方-藿香正气通过调节外周胃肠激素水平,促炎因子和抑炎因子平衡,降低内脏敏感性和改善免疫炎性不平衡状态,从而缓解D-IBS症状,发挥其对于D-IBS的治疗作用。芳香运脾法代表药-藿香是通过多成分、多环节、多靶点的综合作用发挥治疗D-IBS的药效,因此在藿香正气制剂过程中不该随意丢弃主药藿香的有效成分。芳香运脾法则及其代表方药调节应激引发神经-内分泌-免疫网络紊乱,是中医学芳香运脾法调畅中焦脾胃气机、恢复脾胃健运功效的科学内涵之一。该法临床治疗D-IBS切入点与从肝论治---痛泻要方不同,该法则以脾胃升降功能失调为主要病机,适用于以腹泻为主证而伴有腹部不适者。更多还原

【Abstract】 Objective:Irritable bowel syndrome (IBS) is a common disease with gastrointestinal disorder functions, the clinical syndromes include abdominal pain, diarrhea or constipation, and abnormal bowel evacuation habit. It is without changes of structure and biochemistry. The incidence of IBS is very high, but its pathological mechanism is not completely illuminated. At present, the visceral hypersensitivity characterized by changed dynamic and abnormal sense is one of the important pathogenesis. The disharmony of neuroendocrine-immunity network secretion is advanced cognition.The gastrointestinal peptides and cytokines play important roles in the mechanism as middle transmitters. The common treatment is limited to symptomatic, there is no method to root it out now, while Chinese medicine have satisfying curative effect. So there are broad foregrounds of application of traditional Chinese medicine.D-IBS belongs to the category of "diarrhea"、"abdominal pain" in traditional Chinese medicine. Its main mechanism is dysfunction of spleen and stomach, which leads to intestinal secretion of other features missing, liquid water can not infiltrate into the bladder,instead into colon, induce diarrea. Fragrant drugs can regulate the function of spleen and stomach, which has the features of elimination and benefit. Huoxiangzhegnqi is representative of fragrant drugs, which can regulate the activities of qi, eliminate the wetness-evil, invigorate the spleen and the stomach. It has good clinical effect on stopping diarrhea. But there is rare reports of research based on D-IBS. The purpose of our study is to explore the cure effect of Huoxiangzhengqi on D-IBS. By D-IBS rats model, we observe the opsonification of HXZQ on gut hormone and cytokine, in order to elucidate the adjusting visceral hypersensitivity and immunological function. We observe the effect of different ingredients in Agastache rugosa on some gut hormones, to discuss the diverse targets on D-IBS. All of our study will provide the scientific and reliable evidence for clinical application.Methods:1. D-IBS rats model is established by the combination of tied and intragastric administration Folium Cassiae.2. Groups with different concentrations of HXZQ were established. Through testing the changes of the general status such as the body weight, the diarrhea condition, tail flick assay, saccule extension in rectum and colon, we try to explain the effect of HXZQ in adjusting the visceral hypersensitivity preliminarily and determine the best dose.3. The level of SP、VIP、CGRP、ET and CORT were detected by radioimmunoassay and ELISA to show the adjusting effect of HXZQ on gut hormones.4. In order to explore the effect of different ingredients in Agastache rugosa, we detected the level of SP、VIP and ET.5. To discuss the adjusting effect of HXZQ on immunological function, we observed the atrophy degree of the spleen and thoracic gland, detected IL-1βand IL-2.Results:1. D-IBS rats showed obvious diarrhea, weight loss and immunological organs atrophied. There was no obvious injury by light microscope.2. HXZQ may obviously degrade the diarrhea rate (P<0.05), inhibit the weight loss (P<0.01),and improve the abnormal visceral hypersensitivity(P<0.05).The medium dose was the best.3. The medium dose of HXZQ can contribute to adjust the gut hormones, cut down the level of SP、VIP、ET, and keep the expression of CGRP(P>0.05).4. Agastache rugosa also can adjust gut hormones(P<0.05). And different indigents have different effect targets.5. The medium dose of HXZQ can improve the lower immunological conditions, degrade the expression of IL-1β(P<0.05) and elevate the level of IL-2 (P<0.01),except CORT(P>0.05).Conclusions:The model rats can induce the abnormal visceral hypersensitivity and immunological functions under stress. HXZQ, the representative of fragrant drugs, can adjust the expression of gut hormones and cytokines, improve the neuroendocrine-immunity network secretion to educe the therapeutical effect on D-IBS. Different indigents in Agastache rugosa have different effect targets, so in the procedure of making durgs we should not discard any indigent. Yunpi aromatic herbs and their representatives regulating stress-induced nerve-endocrine-immune network disorder, is one of the scientific content of regulating Qi in stomach and spleen, resuming their normal functions. Clinical treatment is different from the Liver pain Diarrhea, diarrhea accompanied by abdominal discomfort were its main syndromes.更多还原