直肠前切除患者术后生活质量调查及5-HT、TRPA1在ARS发病中的作用
发布时间：2018-11-29 08:27
【摘要】：目的前切除综合征(Anterior resection syndrome,ARS)是直肠癌括约肌保留术后病人出现的一个广泛的排便障碍症候群的总称,其发生率高达90%,常见的症状包括便急、便意频繁、排便次数增多、排便不尽感、排便失禁、排便困难等。ARS严重影响患者术后的生活质量目前临床上尚未建立有关ARS的确切定义,且缺乏统一的症状评估标准,其发病机制尚不完全清楚。研究认为新建直肠的容量减少、肠神经系统损伤、自主神经损伤等都是ARS发生的原因。新近的研究发现肠黏膜感觉信号在肠动力紊乱性疾病的发生中发挥重要作用。前切除术后患者突出表现为便意频繁、排便不尽感等症状提示结直肠黏膜感觉功能异常。研究发现肠黏膜瞬时受体电位通道家族的锚蛋白亚家族成员1(transient receptor potential channel-ankyrin subfamily member 1,TRPA1)是存在于肠嗜铬(enterochromaffinl,EC)细胞的感受器分子,可感知肠腔内的物理与化学信号,通过引起Ca2+内流介导EC释放5-羟色胺(5-hydroxytryptamine,5-HT)来调控肠道动力。有关5-HT及TRPA1在ARS发生中的作用迄今未见报道。为此,本课题回顾性分析我院直肠前切除患者术后生活质量、排便功能变化情况,并观察了直肠前切除患者术后吻合口附近直肠的黏膜相关分子感受器表达变化,初步探讨5-HT、TRPA1在前切除患者发病中的作用,为深入研究其病理生理机制提供基础。方法一.研究对象及方法回顾性分析大坪医院胃结直肠肛门外科2012年11月至2014年10月确诊直肠癌行Dixon手术治疗并符合纳入标准的105名患者,通过门诊及电话随访填写术后胃肠道生活质量评分(Gastrointestinal quality of life questionnaire,GIQLI)、Wexner便秘评分(wexner constipation scale,WCS)、Wexner失禁评分(wexner incontinence scale,WIS)及SF-36(the MOS item short from health survey,SF-36)健康问卷,按术后随访时的时间对病人进行分组。其中10例患者在知情同意的前提下愿意进行术后吻合口免疫组化观察,我们取其术前直肠切缘黏膜标本与术后吻合口附近黏膜活检行5-HT、TRPA1免疫组化染色,采用图像分析软件分析免疫组化阳性表达情况。检查前研究对象均签署了知情同意书,本研究经第三军医大学大坪医院野战外科研究所伦理委员会批准。二.检测指标1.直肠前切除术后患者生活质量评分:包括胃肠道生活质量评分、Wexner失禁评分、Wexner便秘评分及SF-36生活质量评分(包括:生理机能、躯体疼痛、社会功能、一般健康状况、精神健康、生理职能、精力、情感职能等8个维度,还包含另一项健康指标:健康变化)。2.直肠吻合口附近黏膜TRPA1受体表达。3.直肠吻合口附近黏膜5-羟色胺表达。结果一.ARS术后患者生活质量评分1.胃肠道生活质量评分:与术后0-6月组的评分相比,术后7-24月组的胃肠道生活质量评分有显著提高(P0.05)。2.Wexner便秘评分:与术后0-6月组的评分相比,术后7-24月组的便秘评分有显著下降(P0.05)。3.Wexner失禁评分:与术后0-6月组的评分相比,术后7-24月组的失禁评分有显著下降(P0.05)。4.SF-36生活健康调查问卷:直肠前切除术后患者SF-36评分中生理机能、生理职能、精力、社会功能、躯体疼痛、情感职能、一般健康状况、精神健康8个子项及健康变化在术后7-24月组均较术后0-6月组有显著改善(P0.05)。二.直肠下段黏膜TRPA1受体表达对比分布于直肠黏膜区域的TRPA1免疫组化阳性表达。与术前组相比,术后ARS患者吻合口上组直肠黏膜TRPA1阳性表达显著降低(P0.05);同时吻合口下组直肠黏膜TRPA1阳性表达也显著降低(P0.05);而吻合口上、下组之间的TRPA1表达未见显著差异(P0.05)。三.直肠下段黏膜5-羟色胺表达对比分布于直肠黏膜区域的5-HT免疫组化阳性表达。与术前组相比,术后ARS患者吻合口上组直肠黏膜5-HT阳性表达显著降低(P0.05);同时吻合口下组直肠黏膜5-HT阳性表达也显著降低(P0.05);而吻合口上、下组之间的5-HT表达未见显著差异(P0.05)。结论通过本课题研究,我们发现直肠前切除患者术后随着时间延长,其胃肠道生活质量、便秘、大便失禁情况以及健康状况等方面有着显著改善。直肠前切除术后的排便功能紊乱可能与直肠黏膜TRPA1表达下调、5-HT表达下调有关,肠黏膜感觉信号异常在ARS发病中的作用机制值得深入研究。
[Abstract]:Objective The anterior resection syndrome (ARS) is a general term of a wide bowel movement disorder in the patients with rectal cancer after the operation of the sphincter of rectal cancer. The incidence rate is up to 90%. The common symptoms include acute and frequent urination, increased defecation frequency, insatiety of defecation, and incontinent. and the like. ARS has a serious effect on the quality of life after operation, and the exact definition of ARS has not been established at present, and there is a lack of unified symptom assessment criteria, and the pathogenesis of ARS is not clear. It is suggested that the reduction of the capacity of the new rectum, the injury of the nervous system, the autonomic nerve injury, etc. are the causes of the ARS. The recent study found that the sensory signal of the intestinal mucosa plays an important role in the pathogenesis of the intestinal motility disorder. After the pre-resection, the patients had the symptoms of frequent occurrence, inexhaustible defecation, and the like, and the sensory function of the colorectal mucosa was abnormal. It was found that the transient receptor potential channel-ankyrin subfamily member 1 (TRPA1) of the transient receptor potential channel family of the intestinal mucosa is a receptor molecule present in the enterochromaffin (EC) cell, and can sense the physical and chemical signals in the intestinal cavity, The intestinal motility was regulated by causing a Ca2 + internal flow-mediated EC to release 5-hydroxytryptamine (5-HT). The role of 5-HT and TRPA1 in the occurrence of ARS has not been reported to date. To this end, this topic is a retrospective analysis of the quality of life and the change of the function of defecation in our hospital, and the changes of the expression of the mucosa-related molecules in the rectum near the anastomotic stoma of the patients with prerectal excision were also observed, and the 5-HT was initially discussed. The role of TRPA1 in the pathogenesis of the pre-resection of the patient is to provide the basis for the in-depth study of its pathophysiological mechanism. Method 1. The subject and method of the study retrospectively analyzed the treatment of the gastric junction of the Daping Hospital from November 2012 to October 2014 and the 105 patients who were included in the standard, and completed the post-operative gastrointestinal life of life score (GQLI) through out-patient and telephone follow-up. The Wexer constipation scale (WCS), the Wexer incontinence scale (WCS), the Wexer incontinence scale (SF-36) and the SF-36 health questionnaire were grouped according to the time at the time of the post-operation follow-up. 10 of the patients were willing to perform the immunohistochemical study on the postoperative anastomotic stoma on the premise of informed consent, and we took the pre-operative transrectal mucosa specimen and the submucosal biopsy in the vicinity of the post-operative anastomotic stoma for 5-HT and TRPA1 immunohistochemical staining, and analyzed the positive expression of the immunohistochemistry by using the image analysis software. The pre-examination subjects signed the informed consent form, and the study was approved by the Ethics Committee of the Field Surgery Research Institute of Daping Hospital of the Third Military Medical University. II. Test indicator 1. Quality of life of the patient after rectocele resection: including the gastrointestinal life quality score, the Wexner incontinence score, the Wexer Constipation score, and the SF-36 life quality score (including: physiological function, body pain, social function, general health, mental health, physiological function, energy, 8 dimensions, such as emotional functions, also include another health indicator: health change). Expression of the submucosal TRPA1 receptor in the vicinity of the rectal anastomosis. The expression of 5-hydroxytryptamine in the adjacent mucosa of the rectum. As a result. The quality of life of patients after ARS was 1. Gastrointestinal life quality score: compared with the score of 0-6 months after operation, there was a significant improvement in the quality of gastrointestinal life in the 7-24 month post-operation group (P0.05). 2. Wexer Constipation Score: There was a significant decrease in the constipation score in the 7-24-month group after the operation (P0.05). There was a significant decrease in the incontinence score in the 7-24-month group after the operation (P0.05). 4. SF-36 Life Health Questionnaire: the physiological function, physical function, energy, social function, physical pain, emotional function, general health status of the patient's SF-36 score after rectocele, compared with the score of the 0-6 month post-operation group. The 8 sub-items and the healthy changes of mental health were significantly improved in the postoperative period from 0 to 6 months after operation (P0.05). II. The expression of TRPA1 receptor in the subrectal mucosa was compared with the immunohistochemical positive expression of TRPA1 in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of TRPA1 in the upper group of the patients with postoperative ARS was significantly lower (P0.05), while the positive expression of TRPA1 in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of TRPA1 between the upper and lower groups of the anastomotic stoma was not found to be significant (P0.05). III. The expression of 5-HT in the subrectal mucosa was compared with the 5-HT immunohistochemical positive expression in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of 5-HT in the upper group of the patients with the postoperative ARS was significantly lower (P0.05), and the expression of 5-HT in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of 5-HT between the upper and lower groups of the anastomotic stoma was not found to be significantly different (P0.05). Conclusion Through this study, we find that the patients with pre-rectal excision have a significant improvement over time, the quality of gastrointestinal life, constipation, fecal incontinence, and the health status of the patients. The disorder of the defecation function after the rectocele resection may be down-regulated with the expression of TRPA1 in the rectal mucosa, and the expression of 5-HT is down-regulated. The mechanism of the abnormal signal of the sensory signal of the intestinal mucosa in the pathogenesis of ARS is worth further study.
【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】：R657.1
[Abstract]:Objective The anterior resection syndrome (ARS) is a general term of a wide bowel movement disorder in the patients with rectal cancer after the operation of the sphincter of rectal cancer. The incidence rate is up to 90%. The common symptoms include acute and frequent urination, increased defecation frequency, insatiety of defecation, and incontinent. and the like. ARS has a serious effect on the quality of life after operation, and the exact definition of ARS has not been established at present, and there is a lack of unified symptom assessment criteria, and the pathogenesis of ARS is not clear. It is suggested that the reduction of the capacity of the new rectum, the injury of the nervous system, the autonomic nerve injury, etc. are the causes of the ARS. The recent study found that the sensory signal of the intestinal mucosa plays an important role in the pathogenesis of the intestinal motility disorder. After the pre-resection, the patients had the symptoms of frequent occurrence, inexhaustible defecation, and the like, and the sensory function of the colorectal mucosa was abnormal. It was found that the transient receptor potential channel-ankyrin subfamily member 1 (TRPA1) of the transient receptor potential channel family of the intestinal mucosa is a receptor molecule present in the enterochromaffin (EC) cell, and can sense the physical and chemical signals in the intestinal cavity, The intestinal motility was regulated by causing a Ca2 + internal flow-mediated EC to release 5-hydroxytryptamine (5-HT). The role of 5-HT and TRPA1 in the occurrence of ARS has not been reported to date. To this end, this topic is a retrospective analysis of the quality of life and the change of the function of defecation in our hospital, and the changes of the expression of the mucosa-related molecules in the rectum near the anastomotic stoma of the patients with prerectal excision were also observed, and the 5-HT was initially discussed. The role of TRPA1 in the pathogenesis of the pre-resection of the patient is to provide the basis for the in-depth study of its pathophysiological mechanism. Method 1. The subject and method of the study retrospectively analyzed the treatment of the gastric junction of the Daping Hospital from November 2012 to October 2014 and the 105 patients who were included in the standard, and completed the post-operative gastrointestinal life of life score (GQLI) through out-patient and telephone follow-up. The Wexer constipation scale (WCS), the Wexer incontinence scale (WCS), the Wexer incontinence scale (SF-36) and the SF-36 health questionnaire were grouped according to the time at the time of the post-operation follow-up. 10 of the patients were willing to perform the immunohistochemical study on the postoperative anastomotic stoma on the premise of informed consent, and we took the pre-operative transrectal mucosa specimen and the submucosal biopsy in the vicinity of the post-operative anastomotic stoma for 5-HT and TRPA1 immunohistochemical staining, and analyzed the positive expression of the immunohistochemistry by using the image analysis software. The pre-examination subjects signed the informed consent form, and the study was approved by the Ethics Committee of the Field Surgery Research Institute of Daping Hospital of the Third Military Medical University. II. Test indicator 1. Quality of life of the patient after rectocele resection: including the gastrointestinal life quality score, the Wexner incontinence score, the Wexer Constipation score, and the SF-36 life quality score (including: physiological function, body pain, social function, general health, mental health, physiological function, energy, 8 dimensions, such as emotional functions, also include another health indicator: health change). Expression of the submucosal TRPA1 receptor in the vicinity of the rectal anastomosis. The expression of 5-hydroxytryptamine in the adjacent mucosa of the rectum. As a result. The quality of life of patients after ARS was 1. Gastrointestinal life quality score: compared with the score of 0-6 months after operation, there was a significant improvement in the quality of gastrointestinal life in the 7-24 month post-operation group (P0.05). 2. Wexer Constipation Score: There was a significant decrease in the constipation score in the 7-24-month group after the operation (P0.05). There was a significant decrease in the incontinence score in the 7-24-month group after the operation (P0.05). 4. SF-36 Life Health Questionnaire: the physiological function, physical function, energy, social function, physical pain, emotional function, general health status of the patient's SF-36 score after rectocele, compared with the score of the 0-6 month post-operation group. The 8 sub-items and the healthy changes of mental health were significantly improved in the postoperative period from 0 to 6 months after operation (P0.05). II. The expression of TRPA1 receptor in the subrectal mucosa was compared with the immunohistochemical positive expression of TRPA1 in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of TRPA1 in the upper group of the patients with postoperative ARS was significantly lower (P0.05), while the positive expression of TRPA1 in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of TRPA1 between the upper and lower groups of the anastomotic stoma was not found to be significant (P0.05). III. The expression of 5-HT in the subrectal mucosa was compared with the 5-HT immunohistochemical positive expression in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of 5-HT in the upper group of the patients with the postoperative ARS was significantly lower (P0.05), and the expression of 5-HT in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of 5-HT between the upper and lower groups of the anastomotic stoma was not found to be significantly different (P0.05). Conclusion Through this study, we find that the patients with pre-rectal excision have a significant improvement over time, the quality of gastrointestinal life, constipation, fecal incontinence, and the health status of the patients. The disorder of the defecation function after the rectocele resection may be down-regulated with the expression of TRPA1 in the rectal mucosa, and the expression of 5-HT is down-regulated. The mechanism of the abnormal signal of the sensory signal of the intestinal mucosa in the pathogenesis of ARS is worth further study.
【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】：R657.1
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