【作者】 于丰彦；

【导师】 周福生；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2009， 博士

【摘要】 肠易激综合征(IBS)是一种常见的以腹痛/腹部不适伴排便习惯改变为特征的功能性肠病,缺乏形态学和生化学改变的生物学标志。IBS的发病机制迄今仍不明确,现在普遍认为是多种因素综合作用的结果,其中心理、精神、社会和环境等因素在发病过程中起重要作用,同时受神经系统、免疫系统和内分泌系统的制约,导致肠道平滑肌运动障碍和内脏感觉异常。在此基础上,当机体受到某些诱因刺激时就会引起肠道易激和过激的功能反应,导致一系列临床症状。其症状发生的直接机制是基于肠道高敏感性和高反应性基础上的肠道运动功能异常。本文通过文献回顾了IBS的发病、致病机理、诊断治疗及几种主要胃肠激素和肥大细胞在IBS致病作用的研究。临床研究通过应用疏肝健脾安神和胃法为组方的康泰方治疗肝郁脾虚型腹泻型IBS患者,进行临床疗效的评估及应用免疫组化检测治疗前、后结肠粘膜肥大细胞表达与SP、VIP、iNOS、HO-1的表达和RT-PCR法检测iNOS、HO-1mRNA的表达,实验证实了疏肝健脾安神和胃法可能通过调控神经-内分泌-免疫调节网络中的肥大细胞和多种胃肠激素而改善临床症状的。目的:1、通过检测肝郁脾虚型腹泻型肠易激综合征患者结肠黏膜iNOS、VIP、SP、HO-1,HO-1mRNA、iNOSmRNA的表达情况及肥大细胞(MC)数量和脱颗粒状况,探讨在肝郁脾虚型腹泻型肠易激综合征发病中的作用和相互关系。2探讨中药康泰方通过影响肝郁脾虚型腹泻型肠易激综合征患者结肠粘膜iNOS、VIP、SP、HO-1,HO-1mRNA、iNOSmRNA的表达情况及肥大细胞(MC)数量和脱颗粒状况而起到治疗作用的可能机理。方法:1、筛选出15名健康志愿者作为健康对照组和63名合格的肝郁脾虚型腹泻型肠易激综合征病例,随机分为康泰方治疗组和得舒特对照药物治疗组,分别给予康泰方和对照药物得舒特治疗,疗程为八周。进行两组治疗前、后临床疗效的评估及对17例康泰方治疗组和16例对照药物治疗组治疗前、后取得了结肠粘膜标本,保留结肠粘膜标本。2、以免疫组化的方法分别检测健康对照组及康泰方治疗组、对照组治疗前、后结肠粘膜肥大细胞(MC)数量和脱颗粒状况及iNOS、VIP、SP、HO-1的表达。3、以RT-PCR的方法检测健康对照组及康泰方治疗组、对照组治疗前、后结肠粘膜HO-1mRNA、iNOSmRNA的表达情况。结果:1、中药康泰方治疗肝郁脾虚型腹泻型IBS总有效率达100%,治疗组的总有效率、痊愈率、显效率均高于对照组。可明显改善IBS的主要临床症状,对照组治疗后腹痛、腹胀、便溏症状较治疗前有所下降,其余各症状积分治疗前后无显著性差异。2、肝郁脾虚型腹泻型IBS结肠粘膜肥大细胞密度及肥大细胞脱颗粒密度以及同时的免疫组化检测SP、VIP、HO-1的表达较正常健康对照组明显增高,iNOS较正常健康对照组明显减低;通过多因素相关因素分析发现肝郁脾虚型腹泻型IBS的主要中医证候和症状,如腹痛、腹胀、便溏、大便不尽感与结肠粘膜肥大细胞密度及肥大细胞脱颗粒密度以及同时的免疫组化检测SP、VIP、HO-1的表达成明显正相关,与iNOS的表达呈负相关。对照组主要中医证候和症状和结肠粘膜肥大细胞密度及肥大细胞脱颗粒密度以及SP、VIP、iNOS、HO-1的表达也存在一定的相关性。3、肝郁脾虚型腹泻型IBS治疗组治疗前和对照组治疗前与正常健康对照组比较,结肠粘膜iNOS、HO-1mRNA的表达呈显著性差异,并与相应的结肠粘膜iNOS、HO-1的表达呈正相关。结论:1、疏肝健脾中药康泰方可明显改善IBS的主要临床症状,在改善心烦失眠、大便不尽感、神疲乏力及胃纳减少等主要中医证候和症状上优于对照组,且没有明显不良反应。2、中药康泰方的应用肝郁脾虚型腹泻型IBS的主要中医证候和症状的改善也同时伴有结肠粘膜肥大细胞密度及肥大细胞脱颗粒密度以及同时的免疫组化检测SP、VIP、HO-1的表达的明显下降和iNOS的升高,并也成正相关关系,而对照组治疗后主要中医证候和症状和结肠粘膜肥大细胞密度及肥大细胞脱颗粒密度以及SP、VIP、iNOS、HO-1的表达也存在一定的相关性。更多还原

【Abstract】 Irritable bowel syndrome is a common functional gastroenteropathy which is the characteristics of abdominal pain/abdominal discomfort and bowel evacuation habit,is short of change of morphology and biochemics.Its pathogenesis isnot clear so far.Now generally agreed that a lot of factors play an important role in clausing smooth muscle dyskinesia and visceral paresthesia,specifically mentality,psyche,society and circumstances,ect.This article reviews the onset,pathopoiesis,diagnosis and treatment of IBS,and relatted to gut hormones and MC to IBS.This clinical study proves Kangtai Fang can improve clinical symptoms by regulating MC and SP、VIP、iNOS、HO-1,ect gut hormones of neuroendocrine-immunization regulating network.Objective:1.By identifying the expression of iNOS,VIP,SP,HO-1,HO-1mRNA,iNOSmRNA and the quantity and degranulation of Mast Cells(MC),to explore the pathogenesis and correlation of irritable bowel syndrome(IBS) with stagnation of liver-QI with deficiency of the spleen and diarrhea.2.By identifying the effectiveness of TCM-Kang Tai Fang to influence the expression of iNOS,VIP,SP,HO-1,HO-1mRNA,iNOSmRNA and the quantity and degranulation of MC of IBS patients with stagnation of liver-QI with deficiency of the spleen and diarrhea,to explore the possible treatment mechanism of Kang Tai Fang.Methods: 1.Screening 15 healthy volunteers as the Control,and 63 qualified irritable bowel syndrome patients with stagnation of liver-QI with deficiency of the spleen and diarrhea randomly grouped as Kang Tai Fang Treatment Group and Dicetel Contrast Group,which are administrated with Kang Tai Fang and Dicetel for 8 weeks,respectively.Record the assessment result of medication effectiveness before and after treatment,obtain and preserve the specimen of colon mucosa of both Kang Tai Fang Treatment Group and Dicetel Contrast Group before and after medication administration.2.Identify the quantity and degranulation of MC and iNOS,VIP,SP,HO-1 expression of the Control,Kang Tai Fang Treatment Group and Dicetel Contrast Group through immunohistochemistry before and after medication administration.3.Identify HO-1mRNA、iNOSmRNA expression of the Control,Kang Tai Fang Treatment Group and Dicetel Contrast Group through RT-PCR before and after medication administration.Results:1.The total effective rate of TCM-Kang Tai Fang is 100%.The total effective rate,cure rate and apparent rate of Kang Tai Fang Treatment Group is significantly higher than Dicetel Contrast Group.TCM-Kang Tai Fang can actively improve the main clinical symptoms of IBS patients,and for Dicetel Contrast Group patients,stomachache,abdominal distension and loose stool can be improved by Dicetel,but others have no obvious improvement.2.Compared to the Control,the IBS patients’ MC density and MC degranulation density,as well as the expression of VIP,SP,HO-1 are significantly increased, iNOS expression is significantly decreased.According to multi-reasons analysis,the positive correlation between IBS patients’ indications and symptoms,such as stomachache,abdominal distention,and loose stool,and the MC density,MC degranulation density,the expression of VIP,SP,HO-1,iNOS is found.For Dicetel Contrast Group patients,the correlation between these aspects is still proved.3.Compared with the Control,the expression of iNOS and HO1mRNA of Kang Tai Fang Treatment Group patients and Dicetel Contrast Group patients is significantly different before and after medication treatment,which is related to the expression of iNOS and HO-1.Conclusions: 1.TCM-Kang Tai Fang can significantly improve IBS patients’ main clinical symptoms without any obvious adverse reaction and its curative effect of improving upset and insomnia,loose stool,debilitation,poor appetite,etc is better than Dicetel.2.For Kang Tai Fang Treatment Group patients,the MC density and MC degranulation density,as well as the expression of VIP,SP,HO-1 are significantly increased,and iNOS expression is significantly decreased.The correlation is positive.In addition,Dicetel can actively play arole on IBS patients’ symptoms and indications,MC density,MC degranulation density,and the expression of VIP,SP,HO-1 and iNOS.更多还原