非糜烂性反流病食管黏膜屏障功能及酸敏感性的研究
发布时间：2019-06-29 12:54
【摘要】：摘要一食管多通道腔内阻抗-pH监测结合酸灌注试验评价非糜烂性反流病食管黏膜屏障功能目的：联合酸灌注试验和24h食管多通道腔内阻抗-pH (MII-pH)监测,研究非糜烂性反流病(NERD)患者酸诱导的食管阻抗动态变化及其与反流症状和食管上皮细胞间隙增宽之间的关系。对象和方法：选取2013年9月至2014年7月我院的NERD患者35例和健康志愿者20例,行24h MII-pH监测、酸灌注试验和胃镜检查。胃镜下在齿状线上2cm,前、后壁各取一块黏膜组织,用软件测量食管上皮细胞间隙。结果：(1)NERD患者食管远端阻抗基线和阻抗恢复速率显著低于健康对照组(2998±701 Ω vs.3880±1054 Ω, P0.01; 30.1±14.0 Ω/min vs.53.0±14.5 Ω/min, P0.01)。(2)阻抗基线与阻抗恢复速率呈显著正相关(r=0.71,P0.01),阻抗基线、阻抗恢复速率分别与AET显著负相关(r=-0.58,P0.01；r=-0.61,P0.01)。(3)酸灌注试验阳性的NERD患者食管阻抗基线和阻抗恢复速率显著低于酸灌注试验阴性的患者(2755±680 Ω vs.3411±536 Ω, P 0.01; 24.9±13.3 Ω/min vs.33.7±10.3 Ω/min,P0.05).。(4)NERD患者食管上皮细胞间隙较健康对照组显著增宽(1.03±0.20 μm vs.0.66±0.14μm, P0.01).阻抗基线、阻抗恢复速率分别与上皮细胞间隙显著负相关(r=-0.68, P0.01;r=-0.67, P0.01). (5) NERD患者食管上皮细胞间隙与烧心和总的症状积分呈显著性正相关(r=0.42, P0.05; r=0.59, P0.05)结论：反复的反流损伤和黏膜修复减慢可能是NERD患者食管黏膜完整性受损的原因。食管阻抗基线的变化一定程度上可反映食管黏膜完整性受损的程度。摘要二非糜烂性反流病食管黏膜组织学结构改变及蛋白酶激活受体-2的表达目的：通过胃镜下黏膜组织活检,研究NERD患者食管上皮组织学结构的改变。运用免疫组织化学的方法,研究蛋白酶激活受体-2(PAR-2)在NERD患者食管黏膜中的表达,分析其与DIS的相关性。对象和方法：选取2013年8月至2014年7月我院的NERD患者59例和健康志愿者20例,行胃镜检查并于齿状线上2cm,食管前、后壁各取一块黏膜组织,苏木精伊红(HE)染色观察食管黏膜组织学形态学改变,包括基底层细胞增生、上皮乳头延长、炎性细胞浸润、上皮细胞气球样变、细胞间隙增宽等；用免疫组织化学的方法检测上皮组织中PAR-2的表达。结果：(1)NERD组和HS组基底层细胞增生检出率分别为84.7%和30.0%,上皮乳头延长分别为49.2%和15.0%,上皮细胞气球样变分别为76.3%和5.0%,炎性细胞浸润分别为35.6%和10.0%。(2)NERD组PAR-2广泛表达于食管上皮细胞。NERD组食管上皮细胞间隙显著增宽(1.00±0.21μm vs.0.67±0.13μm, P0.01),且PAR-2的表达显著高于对照组(6.97±1.73vs.1.45±0.99,P0.01). (3) DIS与PAR-2的表达呈显著正相关(r=0.65,P0.01)。结论：NERD患者食管黏膜存在着一系列组织学结构的改变。PAR-2介导的通路可能通过重新分配紧密连接蛋白引起细胞间隙增宽,参与了NERD的发病机制。摘要三非糜烂性反流病和反流性食管炎症状谱及其相关因素分析目的：通过问卷调查了解NERD和RE患者的一般人口学特点、反流症状谱、饮食习惯、生活质量和精神心理状态等,分析比较两组患者的临床特点,为进一步探讨GERD的发病机制和有效治疗提供依据。对象和方法：本研究纳入105例GERD患者,其中NERD患者60例(男18例,女42例,年龄44.1±13.4岁),RE患者45例(男22例,女23例,年龄46.5±9.9岁)。采用问卷调查的形式对NERD和RE患者的一般人口学特征、症状学特点、饮食和生活习惯、生活质量、精神心理等方面进行分析比较。结果：(1)NERD组反食症状评分和反食症状发生率均低于RE组[0 (0,2) vs.2.0 (0, 3.0),P0.05; 45.0% vs.64.4%, P0.05],两组症状总评分无显著性差异[8.0(6.0,11.0) vs.10.0(7.0,13.0),?0.05]。(2) NERD患者牙痛和龋齿的发生率高于RE组(41.7% vs.8.3%, P0.01; 55.0% vs.8.3%, P0.01),次要症状和食管外症状评分显著高于RE组[4.0(2.0,5.0) vs.2.0(1.0,5.0), P0.05]。 (3) NERD组反流症状的饮食诱因的前五位依次是：奶制品、辛辣饮食、葱或韭菜、甜食、酸奶,除饮食外的其他诱因的前五位依次是：情绪、进食过饱、着凉、餐后弯腰、睡眠不好。(4)NERD合并心理异常组的反流症状积分显著高于无心理异常组(10.9±4.7 vs.8.3±2.8,P0.05)。(5)NERD患者焦虑、抑郁评分与反流症状积分相关(r-0.42,P0.01；r=0.29,P0.05),反流症状积分与GERD-HRQL显著相关(r=0.49,P0.01)。结论：NERD组反食症状较RE组轻,但两组症状总评分无显著性差异。饮食和不良生活习惯在NERD症状发生中起一定作用。NERD患者反流症状和生活质量、精神心理状态显著相关。
[Abstract]:an esophageal multi-channel internal impedance-pH monitoring and acid-perfusion test was used to evaluate the function of non-erosive reflux disease esophageal mucosa barrier: the combined acid-perfusion test and the 24-hour esophageal multi-channel intra-chamber impedance-pH (MII-pH) monitoring, To study the relationship between the dynamic changes of the esophageal impedance induced by acid in the patients with non-erosive reflux disease (NERD) and the relationship between the reflux symptoms and the widening of the gap between the esophageal epithelial cells. Methods:35 cases of NERD and 20 healthy volunteers in our hospital from September 2013 to July 2014 were selected, with 24 h MII-pH monitoring, acid-perfusion and gastroscopy. In the gastroscope,2 cm on the tooth-like line, a mucosal tissue was taken from each of the anterior and posterior walls, and the esophageal epithelial cell gap was measured by software. Results: (1) The baseline and impedance recovery rate of the esophageal far-end impedance of the NERD patients was significantly lower than that in the healthy control group (2998-701惟 vs.3880-1054惟, P0.01; 30.1-14.0 惟/ min vs. 53.0-14.5 惟/ min, P0.01). (2) The impedance baseline and the impedance recovery rate were positively correlated (r = 0.71, P0.01), and the impedance baseline and the impedance recovery rate were negatively correlated with the AET (r =-0.58, P0.01; r =-0.61, P0.01). (3) The baseline and impedance recovery rate of the esophageal impedance of the NERD patients in the acid-perfusion test was significantly lower than those in the negative acid-perfusion test (2755-680惟 vs.3411-536惟, P 0.01; 24.9-13.3 惟/ min vs. 33.7-10.3惟/ min, P0.05). (4) The clearance of the esophageal epithelial cells in the NERD patients was significantly widened in the healthy control group (1.03 to 0.20. mu.m vs. 0.66, 0.14. mu.m, P0.01). Impedance baseline and impedance recovery rate were negatively correlated with the clearance of epithelial cells (r =-0.68, P0.01; r =-0.67, P0.01). (5) There was a significant positive correlation between the esophageal epithelial cell gap (r = 0.42, P0.05; r = 0.59, P0.05) in the NERD patients. The change in the impedance of the esophageal impedance may, to a certain extent, reflect the degree of damage to the integrity of the esophageal mucosa. Objective: To study the changes of the histological structure of the esophageal mucosa and the expression of the protease-activated receptor-2 in the second non-erosive reflux disease. The changes of the structure of the esophageal epithelium of the patients with NERD were studied by the submucosal tissue biopsy under the gastroscope. The expression of protease-activated receptor-2 (PAR-2) in the esophageal mucosa of the patients with NERD was studied by immunohistochemistry, and its correlation with DIS was analyzed. Methods:59 cases of NERD and 20 healthy volunteers from August,2013 to July,2014 were selected. The histological and morphological changes of the esophageal mucosa were observed with hematoxylin and eosin (HE). Including basal layer cell proliferation, epithelial papilla extension, inflammatory cell infiltration, epithelial cell ballooning, cell gap broadening, and the like, and the expression of PAR-2 in the epithelial tissue was detected by immunohistochemistry. Results: (1) The positive rates of cell proliferation in the basal layer of the NERD group and the HS group were 84.7% and 30.0%, respectively. The extension of the epithelial papilla was 49.2% and 15.0%, respectively, and the cell infiltration of the epithelial cells was 76.3% and 5.0%, respectively, and the infiltration of the inflammatory cells was 35.6% and 10.0%, respectively. (2) The PAR-2 in the NERD group is widely expressed in the esophageal epithelial cells. The expression of PAR-2 was significantly higher in the NERD group (1.00-0.21. mu.m vs. 0.67-0.13. mu.m, P0.01), and the expression of PAR-2 was significantly higher than that in the control group (6.97-1.73 vs. 1.45-0.99, P0.01). (3) The expression of DIS and PAR-2 was positively correlated (r = 0.65, P0.01). Conclusion: There is a series of histological changes in the esophageal mucosa of the NERD patients. PAR-2-mediated pathways may be involved in the pathogenesis of NERD by redistributing the close-connexin-inducing cell gap broadening. Objective: To study the general demographic characteristics, reflux symptom spectrum, dietary habit, quality of life and mental state of patients with NERD and RE by questionnaire. The clinical characteristics of the two groups were compared, and the basis for further investigation of the pathogenesis and effective treatment of GERD was provided. Objects and Methods: The study included 105 GERD patients, of which 60 (18 males,42 females, 44.1 to 13.4 years) and 45 RE patients (22 males and 23 females, and 46.5 to 9.9 years) were included in the study. The general demographic characteristics, symptoms, diet and living habits, quality of life and mental psychology of the patients with NERD and RE were compared in the form of questionnaire. Results: (1) The incidence of anti-food symptoms and anti-food symptoms in the NERD group was lower than that of the RE group[0 (0,2) vs. 2.0 (0, 3.0), P0.05; 45.0% vs. 64.4%, P0.05], and there was no significant difference between the two groups (8.0 (6.0, 11.0) vs. 10.0 (7.0, 13.0),? 0.05]. (2) The incidence of toothache and dental caries in the NERD patients was higher than that in the RE group (41.7% vs. 8.3%, P0.01; 55.0% vs. 8.3%, P0.01), and the secondary and out-of-esophageal symptoms were significantly higher than that in the RE group[4.0 (2.0, 5.0) vs. 2.0 (1.0, 5.0), P0.05]. (3) The first five factors of the diet cause of the reflux symptom of the NERD group are: dairy product, spicy food, scallion or leek, sweet, and sour milk, the first five of the other factors other than the diet are: the mood, the eating, the food, the cold, the post-meal stooping, the sleep is not good. (4) The integration of the reflux symptoms in the NERD group was significantly higher than that of the non-psychological abnormality group (10.9% 4.7 vs. 8.3, 2.8, P0.05). (5) The scores of anxiety and depression in the patients with NERD were related to the integration of reflux symptoms (r-0.42, P0.01; r = 0.29, P0.05), and the integration of reflux symptoms was significantly related to GERD-HRQL (r = 0.49, P0.01). Conclusion: The NERD group is lighter than the RE group, but there is no significant difference between the two groups. Diet and bad habits play a role in the occurrence of NERD symptoms. There was a significant correlation between the symptoms of reflux and the quality of life and the mental state of the patients with NERD.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R571
本文编号：2507831
[Abstract]:an esophageal multi-channel internal impedance-pH monitoring and acid-perfusion test was used to evaluate the function of non-erosive reflux disease esophageal mucosa barrier: the combined acid-perfusion test and the 24-hour esophageal multi-channel intra-chamber impedance-pH (MII-pH) monitoring, To study the relationship between the dynamic changes of the esophageal impedance induced by acid in the patients with non-erosive reflux disease (NERD) and the relationship between the reflux symptoms and the widening of the gap between the esophageal epithelial cells. Methods:35 cases of NERD and 20 healthy volunteers in our hospital from September 2013 to July 2014 were selected, with 24 h MII-pH monitoring, acid-perfusion and gastroscopy. In the gastroscope,2 cm on the tooth-like line, a mucosal tissue was taken from each of the anterior and posterior walls, and the esophageal epithelial cell gap was measured by software. Results: (1) The baseline and impedance recovery rate of the esophageal far-end impedance of the NERD patients was significantly lower than that in the healthy control group (2998-701惟 vs.3880-1054惟, P0.01; 30.1-14.0 惟/ min vs. 53.0-14.5 惟/ min, P0.01). (2) The impedance baseline and the impedance recovery rate were positively correlated (r = 0.71, P0.01), and the impedance baseline and the impedance recovery rate were negatively correlated with the AET (r =-0.58, P0.01; r =-0.61, P0.01). (3) The baseline and impedance recovery rate of the esophageal impedance of the NERD patients in the acid-perfusion test was significantly lower than those in the negative acid-perfusion test (2755-680惟 vs.3411-536惟, P 0.01; 24.9-13.3 惟/ min vs. 33.7-10.3惟/ min, P0.05). (4) The clearance of the esophageal epithelial cells in the NERD patients was significantly widened in the healthy control group (1.03 to 0.20. mu.m vs. 0.66, 0.14. mu.m, P0.01). Impedance baseline and impedance recovery rate were negatively correlated with the clearance of epithelial cells (r =-0.68, P0.01; r =-0.67, P0.01). (5) There was a significant positive correlation between the esophageal epithelial cell gap (r = 0.42, P0.05; r = 0.59, P0.05) in the NERD patients. The change in the impedance of the esophageal impedance may, to a certain extent, reflect the degree of damage to the integrity of the esophageal mucosa. Objective: To study the changes of the histological structure of the esophageal mucosa and the expression of the protease-activated receptor-2 in the second non-erosive reflux disease. The changes of the structure of the esophageal epithelium of the patients with NERD were studied by the submucosal tissue biopsy under the gastroscope. The expression of protease-activated receptor-2 (PAR-2) in the esophageal mucosa of the patients with NERD was studied by immunohistochemistry, and its correlation with DIS was analyzed. Methods:59 cases of NERD and 20 healthy volunteers from August,2013 to July,2014 were selected. The histological and morphological changes of the esophageal mucosa were observed with hematoxylin and eosin (HE). Including basal layer cell proliferation, epithelial papilla extension, inflammatory cell infiltration, epithelial cell ballooning, cell gap broadening, and the like, and the expression of PAR-2 in the epithelial tissue was detected by immunohistochemistry. Results: (1) The positive rates of cell proliferation in the basal layer of the NERD group and the HS group were 84.7% and 30.0%, respectively. The extension of the epithelial papilla was 49.2% and 15.0%, respectively, and the cell infiltration of the epithelial cells was 76.3% and 5.0%, respectively, and the infiltration of the inflammatory cells was 35.6% and 10.0%, respectively. (2) The PAR-2 in the NERD group is widely expressed in the esophageal epithelial cells. The expression of PAR-2 was significantly higher in the NERD group (1.00-0.21. mu.m vs. 0.67-0.13. mu.m, P0.01), and the expression of PAR-2 was significantly higher than that in the control group (6.97-1.73 vs. 1.45-0.99, P0.01). (3) The expression of DIS and PAR-2 was positively correlated (r = 0.65, P0.01). Conclusion: There is a series of histological changes in the esophageal mucosa of the NERD patients. PAR-2-mediated pathways may be involved in the pathogenesis of NERD by redistributing the close-connexin-inducing cell gap broadening. Objective: To study the general demographic characteristics, reflux symptom spectrum, dietary habit, quality of life and mental state of patients with NERD and RE by questionnaire. The clinical characteristics of the two groups were compared, and the basis for further investigation of the pathogenesis and effective treatment of GERD was provided. Objects and Methods: The study included 105 GERD patients, of which 60 (18 males,42 females, 44.1 to 13.4 years) and 45 RE patients (22 males and 23 females, and 46.5 to 9.9 years) were included in the study. The general demographic characteristics, symptoms, diet and living habits, quality of life and mental psychology of the patients with NERD and RE were compared in the form of questionnaire. Results: (1) The incidence of anti-food symptoms and anti-food symptoms in the NERD group was lower than that of the RE group[0 (0,2) vs. 2.0 (0, 3.0), P0.05; 45.0% vs. 64.4%, P0.05], and there was no significant difference between the two groups (8.0 (6.0, 11.0) vs. 10.0 (7.0, 13.0),? 0.05]. (2) The incidence of toothache and dental caries in the NERD patients was higher than that in the RE group (41.7% vs. 8.3%, P0.01; 55.0% vs. 8.3%, P0.01), and the secondary and out-of-esophageal symptoms were significantly higher than that in the RE group[4.0 (2.0, 5.0) vs. 2.0 (1.0, 5.0), P0.05]. (3) The first five factors of the diet cause of the reflux symptom of the NERD group are: dairy product, spicy food, scallion or leek, sweet, and sour milk, the first five of the other factors other than the diet are: the mood, the eating, the food, the cold, the post-meal stooping, the sleep is not good. (4) The integration of the reflux symptoms in the NERD group was significantly higher than that of the non-psychological abnormality group (10.9% 4.7 vs. 8.3, 2.8, P0.05). (5) The scores of anxiety and depression in the patients with NERD were related to the integration of reflux symptoms (r-0.42, P0.01; r = 0.29, P0.05), and the integration of reflux symptoms was significantly related to GERD-HRQL (r = 0.49, P0.01). Conclusion: The NERD group is lighter than the RE group, but there is no significant difference between the two groups. Diet and bad habits play a role in the occurrence of NERD symptoms. There was a significant correlation between the symptoms of reflux and the quality of life and the mental state of the patients with NERD.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R571
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