慢传输型便秘手术疗效评估及结肠粘膜5-HT、TRPA1与TRPV1表达变化研究

发布时间：2018-07-27 18:09

【摘要】：背景慢传输型便秘(slow transit constipation,STC)是由于结肠传输功能障碍,肠内容物滞留所引起的一种常见的功能性便秘类型。临床症状顽固,保守治疗效果不佳,手术切除无力结肠是最终的选择。目前,全结肠切除回直吻合术(ileorectal anastomosis,IRA)与次全结肠切除盲直吻合术(cecorectal anastomosis,CRA)是外科治疗STC应用最常用的手术方式。手术治疗STC尽管取得了较满意的临床结局,但其术后排便功能及生活质量的改善状况少有报道。同时,一些术后出现的顽固性腹泻、便秘复发、粘连性肠梗阻等并发症仍是影响手术治疗的负面因素。然而,国内外相关研究报道较少,且多为小样本回顾性研究。因此,研究STC患者术后疗效、排便功能、生活质量对进一步改进STC的外科治疗具有重要的临床意义。另外,STC作为一种功能性肠动力障碍,手术治疗是内科治疗失败后的无奈选择,如果能够阐明其病理生理机制,对STC的防治将具有重大的推动意义。近年来,有研究报道肠粘膜感觉信号在调控肠道动力方面发挥重要作用。STC患者临床上突出地表现为无便意,及无主观排便感觉,结肠传输功能障碍,提示肠粘膜感觉功能异常可能在其发病机制中发挥作用。有研究发现,瞬时受体电位通道A1(transient receptor potential channel-ankyrin subfamily member 1,TRPA1)是肠嗜铬细胞(enterochromaffin cell,ECC)的感受器分子,可感知肠腔内物理与化学信号,介导ECC释放5-羟色胺(5-hydroxytryptamine,5-HT)调控肠道动力。另有研究结果表明,瞬时受体电位通道V1(transient receptor potential channel-vanilloid subfamily member 1,TRPV1)在肠粘膜感觉神经调控肠动力中发挥重要作用,同时,大量研究发现TRPA1与TRPV1在诸多神经与非神经组织上存在协同作用。那么,TRPA1与TRPV1在STC患者结肠粘膜表达是否异常,迄今为止,国内外未见报道。从肠粘膜感觉神经调控切入初步探讨STC的发病机制具有重要意义。目的1、回顾性分析stc患者一般资料,对患者术后疗效、排便功能及生活质量改善状况进行评估;2、观察stc患者降结肠粘膜trpa1、trpv1与5-ht的表达变化,初步探讨其在stc发病中的作用。方法选取大坪医院普通外科中心胃结直肠肛门外科2007年8月至2015年2月明确诊断stc并行手术治疗患者38例作为研究对象,成功随访29例患者,失访9例(7例失访、1例拒绝接受随访、1例死于呼吸系统疾病合并呼吸衰竭)。所有研究对象均通过胃肠道生活质量评分(gastrointestinalqualityoflifeindex,giqli)、wexner便秘评分(wexnerconstipation,wc)、wexner大便失禁评分(wexnerincontinence,wi)及sf-36健康调查问卷(36-itemshort-formhealthsurvey,sf-36)进行评估,分析手术疗效及生活质量变化情况。同时,收集大坪医院普通外科中心胃结直肠肛门外科2013年3月至2014年3月收治的10例stc患者手术切除的降结肠标本为stc组,及2013年12月至2014年5月收治的10例乙状结肠癌患者手术切除的降结肠标本(距肿瘤边缘10cm以上)为对照组。采用免疫荧光双标检测对照组结肠粘膜中trpa1与色氨酸羟化酶(tryptophanhydroxylase,tph)、trpv1与tph表达情况,免疫组化检测两组trpa1、trpv1与5-ht表达情况,westernblot检测两组trpa1与trpv1表达情况。所有纳入研究对象均签署知情同意书。结果一、stc患者临床资料分析及术后疗效评估1、术后并发症及排便功能:1例患者因呼吸系统疾病合并呼吸衰竭死亡。术后4例(13.8%)患者出现炎性肠梗阻,保守治疗治愈;2例患者术后出现肺部感染,其中1例为腹腔和肺部感染,这是由于出现了十二指肠瘘,再次手术修补十二指肠瘘治愈。3例(10.3%)患者出现远期并发症,其中粘连性肠梗阻2例,再次入院行肠粘黏松解术治愈;便秘复发2例;吻合口狭窄1例。与术前相比,stc患者术后3月每周排便次数即显著增加(p0.01),术后排便费劲、腹胀及泻剂使用情况均显著改善(p0.01),89.7%患者表示手术对其健康变化有益;2、wexner失禁评分:与术后3月相比,stc患者术后6月、1-2年及2-7年wi分值均无统计学差异(p0.05);3、wexner便秘评分:与术前相比,stc患者术后3月、6月、1-2年及2-7年wc分值均较术前显著改善(p0.01);4、胃肠道生活质量评分:与术前相比,STC患者术后3月、6月、1-2年及2-7年GIQLI分值均较术前显著改善(P0.01);5、SF-36健康调查问卷:与术前相比,STC患者术后1-2年生活质量在生理职能、情感职能、躯体疼痛、精力、精神健康、社会功能及一般健康状况等7个方面有显著改善(P0.05);术后2-7年生活质量在生理职能、情感职能、躯体疼痛、精力及社会功能方面有显著改善(P0.05)。二、STC患者降结肠粘膜TRPA1、TRPV1与5-HT表达情况1、免疫荧光双标检测发现TRPA1与TPH、TRPV1与TPH在人的结肠粘膜ECC上共表达;2、免疫组化染色检测发现:与对照组相比,STC组降结肠粘膜TRPA1与TRPV1表达水平下调(P0.05),而5-HT表达水平上调(P0.05);3、Western Blot检测发现:与对照组相比,STC组降结肠粘膜TRPA1与TRPV1表达水平下调(P0.05)。结论1、结肠全或次全切除手术治疗STC是一个有效且能被大部分患者所接受的治疗方案,它不仅在近期内能显著改善患者的便秘临床症状,而且随着时间推移,生活质量也有显著提高;2、TRPA1与TRPV1均在肠ECC上表达,提示TRPA1与TRPV1介导ECC释放5-HT调控肠道动力;STC降结肠粘膜TRPA1与TRPV1表达下调,5-HT表达上调,提示肠粘膜感觉信号传入障碍可能与STC发病机制相关。
[Abstract]:Background slow transit constipation (slow transit constipation, STC) is a common type of functional constipation caused by colon transmission dysfunction and retention of intestinal contents. Clinical symptoms are stubborn, conservative treatment is not effective, surgical removal of the colon is the ultimate choice. Currently, total colectomy and direct anastomosis (ileorectal anastom) Osis, IRA) and subtotal colectomy blind direct anastomosis (cecorectal anastomosis, CRA) is the most commonly used surgical method for the surgical treatment of STC. Although the surgical treatment of STC has achieved a satisfactory clinical outcome, the postoperative defecation function and the improvement of the quality of life are rarely reported. At the same time, some of the postoperative intractable diarrhea and constipation are recovered. Complications such as hair and adhesive ileus are still the negative factors affecting the surgical treatment. However, there are few related reports at home and abroad, and most of them are small sample retrospective studies. Therefore, the study of postoperative curative effect, defecation function and quality of life of STC patients has important clinical significance for the further improvement of the surgical treatment of STC. In addition, STC is a kind of work. Dysfunctional intestinal motility disorder, surgical treatment is a helpless choice after internal medical treatment failure. If it can clarify its pathophysiological mechanism, it will have great significance for the prevention and control of STC. In recent years, there has been a research report that intestinal mucosal sensory signals play an important role in regulating intestinal motility, and.STC patients are clinically prominent in clinical. It is found that the transient receptor potential channel A1 (transient receptor potential channel-ankyrin subfamily member 1, TRPA1) is a receptor molecule of intestinal chromaffin cells (enterochromaffin cell, ECC). We can perceive the physical and chemical signals in the intestinal cavity and mediate the release of 5- hydroxytryptamine (5-hydroxytryptamine, 5-HT) by ECC to regulate intestinal motility. The results show that the instantaneous receptor potential channel V1 (transient receptor potential channel-vanilloid subfamily member 1, TRPV1) plays an important role in intestinal motility in the intestinal mucosa. At the same time, a large number of studies have found that there is a synergistic effect between TRPA1 and TRPV1 in many nerve and non nerve tissue. Then, the expression of TRPA1 and TRPV1 in the colon mucosa of STC patients is abnormal, so far, no reports have been reported at home and abroad. It is of great significance to explore the pathogenesis of STC from the regulation of the sensory nerve of the intestinal mucosa. 1 The general data of STC patients were evaluated for postoperative curative effect, defecation function and improvement of quality of life. 2, the changes in the expression of TRPA1, TRPV1 and 5-HT in the descending colon mucosa of patients with STC were observed, and their role in the pathogenesis of STC was preliminarily discussed. Methods the cardiac and gastric colorectal anus surgery in Daping Hospital was selected from August 2007 to February 2015. 38 patients were treated with STC, 29 patients were followed up, 9 cases were lost (7 cases were lost, 1 refused to follow up, 1 died of respiratory failure with respiratory failure). All the subjects were evaluated by gastrointestinalqualityoflifeindex (GIQLI) and Wexner constipation score (wexnercon Stipation, WC), Wexner (wexnerincontinence, WI) and SF-36 Health Questionnaire (36-itemshort-formhealthsurvey, SF-36) to evaluate the effect and quality of life. At the same time, 10 cases of STC patients in the general surgical center of Daping Hospital were collected from March 2013 to March 2014. The resected specimens of descending colon were in group STC, and 10 cases of colon cancer patients treated from December 2013 to May 2014 were treated with surgical resection of the descending colon (above the tumor margin 10cm) as the control group. The TRPA1 and tryptophan hydroxylase (tryptophanhydroxylase, TPH), TRPV1 and TPH in the colon mucosa of the control group were detected by double immunofluorescence The expression of two groups of TRPA1, TRPV1 and 5-HT were detected by immunohistochemistry, and the expression of TRPA1 and TRPV1 in two groups was detected by Westernblot. All the subjects included in the study signed the informed consent. Results 1, the analysis of clinical data and postoperative efficacy assessment of STC patients 1, postoperative complications and defecation function: 1 patients were associated respiratory failure due to respiratory diseases. After operation, 4 cases (13.8%) had inflammatory bowel obstruction, conservative treatment and 2 cases of postoperative pulmonary infection, including 1 cases of abdominal and pulmonary infection, which was due to the appearance of duodenal fistula, and reoperation of duodenal fistula to cure.3 (10.3%) patients with long-term complications, of which 2 cases of adhesive ileus were re entered. There were 2 cases of constipation, 2 cases of constipation and 1 cases of anastomotic stenosis. Compared with preoperative, the number of defecation in STC patients increased significantly (P0.01) in March, postoperative defecation was hard, abdominal distention and laxative use were significantly improved (P0.01), and 89.7% patients were beneficial to their health changes; 2, Wexner incontinence score: 3 month postoperatively. STC patients had no statistically significant difference (P0.05), 3, and Wexner constipation scores in June, 1-2 and 2-7 years postoperatively. Compared with preoperative, STC patients were significantly improved in March, June, 1-2 and 2-7 years than before operation (P0.01); 4, GI quality score: compared with preoperative, STC patients were compared with surgery in March, June, 1-2 and 2-7 years. Pre significant improvement (P0.01); 5, SF-36 Health Questionnaire: compared with preoperative, the quality of life in 1-2 years after operation in STC patients was significantly improved in 7 aspects of physiological function, emotional function, body pain, energy, mental health, social function and general health status (P0.05), and the quality of life after 2-7 years was in physiological function, emotional function, somatic pain, and essence. There was a significant improvement in the force and social function (P0.05). Two, the expression of TRPA1, TRPV1 and 5-HT in the descending colon mucosa of STC patients was 1. The double immunofluorescence double labeling detected the expression of TRPA1 and TPH, TRPV1 and TPH were co expressed on the colon mucosa of the human colon mucous membrane; 2, immunohistochemical staining found that the lower colon mucosa TRPA1 and expression level of STC group were compared with those in the control group. (P0.05), and 5-HT expression level up (P0.05); 3, Western Blot detection found that compared with the control group, the TRPA1 and TRPV1 expression level of the colon mucosa decreased (P0.05) in the STC group. Conclusion 1, full or subtotal colectomy for STC is an effective and acceptable treatment for most patients. It can not only be significantly improved in the near future. The clinical symptoms of constipation and the quality of life improved significantly over time; 2, both TRPA1 and TRPV1 were expressed on the intestinal ECC, suggesting that TRPA1 and TRPV1 mediated ECC release 5-HT to regulate intestinal motility; the expression of TRPA1 and TRPV1 in the mucosa of STC descending colon mucosa was down regulated, and 5-HT expression was up regulated, suggesting that the sensory afferent disorder in intestinal mucosa may be associated with STC pathogenesis. The system is related.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R656.9

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