【摘要】：背景慢傳輸型便秘(slow transit constipation,STC)是由于結腸傳輸功能障礙,腸內容物滯留所引起的一種常見的功能性便秘類型。臨床癥狀頑固,保守治療效果不佳,手術切除無力結腸是最終的選擇。目前,全結腸切除回直吻合術(ileorectal anastomosis,IRA)與次全結腸切除盲直吻合術(cecorectal anastomosis,CRA)是外科治療STC應用最常用的手術方式。手術治療STC盡管取得了較滿意的臨床結局,但其術后排便功能及生活質量的改善狀況少有報道。同時,一些術后出現(xiàn)的頑固性腹瀉、便秘復發(fā)、粘連性腸梗阻等并發(fā)癥仍是影響手術治療的負面因素。然而,國內外相關研究報道較少,且多為小樣本回顧性研究。因此,研究STC患者術后療效、排便功能、生活質量對進一步改進STC的外科治療具有重要的臨床意義。另外,STC作為一種功能性腸動力障礙,手術治療是內科治療失敗后的無奈選擇,如果能夠闡明其病理生理機制,對STC的防治將具有重大的推動意義。近年來,有研究報道腸粘膜感覺信號在調控腸道動力方面發(fā)揮重要作用。STC患者臨床上突出地表現(xiàn)為無便意,及無主觀排便感覺,結腸傳輸功能障礙,提示腸粘膜感覺功能異�？赡茉谄浒l(fā)病機制中發(fā)揮作用。有研究發(fā)現(xiàn),瞬時受體電位通道A1(transient receptor potential channel-ankyrin subfamily member 1,TRPA1)是腸嗜鉻細胞(enterochromaffin cell,ECC)的感受器分子,可感知腸腔內物理與化學信號,介導ECC釋放5-羥色胺(5-hydroxytryptamine,5-HT)調控腸道動力。另有研究結果表明,瞬時受體電位通道V1(transient receptor potential channel-vanilloid subfamily member 1,TRPV1)在腸粘膜感覺神經調控腸動力中發(fā)揮重要作用,同時,大量研究發(fā)現(xiàn)TRPA1與TRPV1在諸多神經與非神經組織上存在協(xié)同作用。那么,TRPA1與TRPV1在STC患者結腸粘膜表達是否異常,迄今為止,國內外未見報道。從腸粘膜感覺神經調控切入初步探討STC的發(fā)病機制具有重要意義。目的1、回顧性分析stc患者一般資料,對患者術后療效、排便功能及生活質量改善狀況進行評估;2、觀察stc患者降結腸粘膜trpa1、trpv1與5-ht的表達變化,初步探討其在stc發(fā)病中的作用。方法選取大坪醫(yī)院普通外科中心胃結直腸肛門外科2007年8月至2015年2月明確診斷stc并行手術治療患者38例作為研究對象,成功隨訪29例患者,失訪9例(7例失訪、1例拒絕接受隨訪、1例死于呼吸系統(tǒng)疾病合并呼吸衰竭)。所有研究對象均通過胃腸道生活質量評分(gastrointestinalqualityoflifeindex,giqli)、wexner便秘評分(wexnerconstipation,wc)、wexner大便失禁評分(wexnerincontinence,wi)及sf-36健康調查問卷(36-itemshort-formhealthsurvey,sf-36)進行評估,分析手術療效及生活質量變化情況。同時,收集大坪醫(yī)院普通外科中心胃結直腸肛門外科2013年3月至2014年3月收治的10例stc患者手術切除的降結腸標本為stc組,及2013年12月至2014年5月收治的10例乙狀結腸癌患者手術切除的降結腸標本(距腫瘤邊緣10cm以上)為對照組。采用免疫熒光雙標檢測對照組結腸粘膜中trpa1與色氨酸羥化酶(tryptophanhydroxylase,tph)、trpv1與tph表達情況,免疫組化檢測兩組trpa1、trpv1與5-ht表達情況,westernblot檢測兩組trpa1與trpv1表達情況。所有納入研究對象均簽署知情同意書。結果一、stc患者臨床資料分析及術后療效評估1、術后并發(fā)癥及排便功能:1例患者因呼吸系統(tǒng)疾病合并呼吸衰竭死亡。術后4例(13.8%)患者出現(xiàn)炎性腸梗阻,保守治療治愈;2例患者術后出現(xiàn)肺部感染,其中1例為腹腔和肺部感染,這是由于出現(xiàn)了十二指腸瘺,再次手術修補十二指腸瘺治愈。3例(10.3%)患者出現(xiàn)遠期并發(fā)癥,其中粘連性腸梗阻2例,再次入院行腸粘黏松解術治愈;便秘復發(fā)2例;吻合口狹窄1例。與術前相比,stc患者術后3月每周排便次數(shù)即顯著增加(p0.01),術后排便費勁、腹脹及瀉劑使用情況均顯著改善(p0.01),89.7%患者表示手術對其健康變化有益;2、wexner失禁評分:與術后3月相比,stc患者術后6月、1-2年及2-7年wi分值均無統(tǒng)計學差異(p0.05);3、wexner便秘評分:與術前相比,stc患者術后3月、6月、1-2年及2-7年wc分值均較術前顯著改善(p0.01);4、胃腸道生活質量評分:與術前相比,STC患者術后3月、6月、1-2年及2-7年GIQLI分值均較術前顯著改善(P0.01);5、SF-36健康調查問卷:與術前相比,STC患者術后1-2年生活質量在生理職能、情感職能、軀體疼痛、精力、精神健康、社會功能及一般健康狀況等7個方面有顯著改善(P0.05);術后2-7年生活質量在生理職能、情感職能、軀體疼痛、精力及社會功能方面有顯著改善(P0.05)。二、STC患者降結腸粘膜TRPA1、TRPV1與5-HT表達情況1、免疫熒光雙標檢測發(fā)現(xiàn)TRPA1與TPH、TRPV1與TPH在人的結腸粘膜ECC上共表達;2、免疫組化染色檢測發(fā)現(xiàn):與對照組相比,STC組降結腸粘膜TRPA1與TRPV1表達水平下調(P0.05),而5-HT表達水平上調(P0.05);3、Western Blot檢測發(fā)現(xiàn):與對照組相比,STC組降結腸粘膜TRPA1與TRPV1表達水平下調(P0.05)。結論1、結腸全或次全切除手術治療STC是一個有效且能被大部分患者所接受的治療方案,它不僅在近期內能顯著改善患者的便秘臨床癥狀,而且隨著時間推移,生活質量也有顯著提高;2、TRPA1與TRPV1均在腸ECC上表達,提示TRPA1與TRPV1介導ECC釋放5-HT調控腸道動力;STC降結腸粘膜TRPA1與TRPV1表達下調,5-HT表達上調,提示腸粘膜感覺信號傳入障礙可能與STC發(fā)病機制相關。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R656.9

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