肥胖相关基因UCP2在Barrett食管粘膜中表达变化及临床意义的研究

  本文关键词：肥胖相关基因UCP2在Barrett食管粘膜中表达变化及临床意义的研究，由笔耕文化传播整理发布。

        目的1. UCP2蛋白在正常食管、反流性食管炎，Barrett食管和食管腺癌的食管粘膜中表达变化的研究。2. UCP2蛋白在Barrett食管粘膜中表达与BMI和WC的关系,并探讨其临床意义。方法1.记录患者一般情况，包括其年龄、性别、病程、症状等，其中症状包括：反酸或反流、烧心、上腹部不适或疼痛、吞咽困难，消化道外症状(如咳嗽，咽部不适包括咽炎、癔球症等)。并记录患者的身高、体重和臀围。2.胃镜下每位患者分别于四个象限各取活检一块，活检标本分为两份，一份放入中性福尔马林中固定，另一份快速放入液氮中保存。3.实验分为正常对照组、RE组、BE组和EAC组，并根据BMI的大小分为BMI≥24和BMI<24两个亚组，根据WC的大小分为WC≥80/85（女/男）和WC<80/85（女/男）两个亚组。4.用免疫组织化学方法检测对照组和病例组食管粘膜中TGF-β、UCP2的表达，黄嘌呤氧化酶法测定SOD活力，硫代巴比妥酸显色法检测血浆MDA含量。结果1.正常对照组、RE组、BE组和EAC组血浆MDA含量呈增加趋势，各组差异有统计学意义（P<0.05）,血浆SOD活力逐渐降低，正常对照组和各病例组差异有统计学意义（P<0.05)，但RE组和BE组以及BE组和EAC组差异没有统计学意义（P>0.05）。2.各组均表达TGF-β1，按对照组，RE组、BE组和EAC组顺序,粘膜上皮中TGF-β1蛋白的表达量逐渐增加，但差异无统计学意义（P>0.05）；正常对照组无UCP2蛋白表达，，RE组、BE组和EAC组UCP2蛋白的表达量逐渐增加，各组差异有统计学意义（P<0.05)。3.对BMI<24和BMI≥24及WC≥80/85（女/男）和WC<80/85（女/男）亚组患者食管粘膜中UCP2表达量进行卡方检验。随BMI增加，UCP2表达降低，但差异无统计学意义（P>0.05）；WC增加，UCP2表达降低，RE组、BE组和病例组差异有统计学意义（P<0.05）;并对患者食管粘膜UCP2的表达和患者BMI、WC的大小进行相关性分析，得出患者WC和UCP2表达的相关系数r=-0.889，P=0.000,BMI和UCP2表达的r=-0.102, P=0.237，说明WC的大小和UCP2的表达相关性更强。4. BMI的增加，增加了反酸或反流、上腹部不适或疼痛和恶心等胃食管反流病症状的发生率，但BMI≥24较BMI<24的患者上述症状出现的频率差异无统计学意义（P>0.05）；烧心症状在两组间差异有统计学意义（P<0.05）。较WC<80/85(女/男)患者，WC≥80/85(女/男)的患者反酸或反流、烧心、上腹部不适或疼痛等症状均增加，且差异有统计学意义（P<0.05）。将GERD细分为RE、BE两组后，随着BMI和WC的增加，同样也增加了患者反酸或反流，烧心，上腹部不适或疼痛和恶心等症状的发生率。但WC的大小较BMI的大小对症状的影响更明显。结论肥胖Barrett食管患者食管粘膜中UCP2表达降低，同时肥胖尤其是腹型肥胖增加了Barrett食管的发病风险，并使Barrett食管患者的反酸，烧心等症状的加重。但是否UCP2表达降低导致肥胖，进而使Barrett食管发生的风险增加，还有待进一步研究。

    Objectives1. Investigate the expression of UCP2in reflux esophagitis, Barrett esophagus andesophageal adenocarcinoma.2. To assess the relationship between UCP2and BMI、WC in the Barrett’sesophagus.Material and Methods1. Collection and recording the clinical data, including age, gender, process andsymptoms, the symptoms include: acid reflux, heart burn, upper abdominaldiscomfort or pain, swallowing difficulties, extraesophageal symptom (such ascough, throat discomfort including pharyngitis, hysteria ball),and record thepatient’s height, weight and hip.2. Each patient were taken four specimens were divided into two, one into theNeutral formalin, another stored in liquid nitrogen.3. From January2010to June2011,145subjects were enrolled(30in control group,60in reflux esophagitis,45in Barrett esophagus and10in esophagealadenocarcinoma).Subproups were divided according to BMI and WC.4. Analyze the levels of MDA and SOD with thiobarbituric acid cololimitric method and xanthine oxidase method. The expression levels of TGF-β and UCP2protein in the esophageal mucosa tissue of normal control group and patients withreflux esophagitis, Barrett esophagus and esophageal adenocarcinoma weredetected by Immunohistochemistry (IHC).Results1. The levels of MDA increased progressing with the development of refluxesophagitis, into Barrett esophagus and esophageal adenocarcinoma（P<0.05),andSOD activity decreased,but there is no significance between reflux esophagitisand Barrett esophagus,and Barrett esophagus and esophageal adenocarcinoma(P>0.05).2. The levels of TGF-β increased progressing with the development of refluxesophagitis, into Barrett esophagus and esophageal adenocarcinoma,but therewas no statistically significan(P>0.05).There was no UCP2protein expression innormal squamous esophagus and increased progressing with the development ofreflux esophagitis, into Barrett esophagus and esophageal adenocarcinoma,andthere was statistically significant（P<0.05).3. The expression level of UCP2was decreased along with the increase of BMI;InRE, BE and case groups, the UCP2was significantly decreased along with theincrease of WC (P<0.05). Correlation analysis showed that the expression level ofUCP2was negatively related with WC (r=-0.889, P=0.00) and BMI (r=-0.102,P=0.237), suggesting WC has more significant correlation with the expressionlevel of UCP2.4. Relationship between obesity and BE the symptoms of GERD, including reflux ofgastric acid, upper abdominal discomfort or pain, nausea, were increased alongwith the increase of BMI, however, there was no significant difference between BMI≥24and BMI <24groups (P>0.05). The symptom of heartburn wassignificant different between these two groups (P <0.05). The symptoms of refluxof gastric acid, heartburn and upper abdominal discomfort or pain weresignificantly increased in patients of WC≥80/85(female/male) group, comparedwith those in patients of WC<80/85(female/male) group. After dividing theGERD to RE and BE groups, the symptoms of reflux of gastric acid, heartburn,upper abdominal discomfort or pain and nausea were increased along with theincrease of BMI and WC. However, WC affected the symptoms more thanBMI.ConclusionThe UCP2expression decreased in obesity Barrett’s esophagus, obesityespecially abdominal obesity increasing the risk of Barrett’s esophagus disease, andto increase in acid reflux, heartburn and other symptoms of Barrett’s esophagus. Butwhether it is the expression of UCP2reduce the lead to obesity, which led to Barrett’sesophagus, there are to be further verified.

肥胖相关基因UCP2在Barrett食管粘膜中表达变化及临床意义的研究

摘要5-8ABSTRACT8-10前言11-14第一部分：UCP2 在反流性食管炎、Barrett 食管和食管腺癌粘膜中表达差异的研究14-33    材料与方法15-24    结果24-31    讨论31-33第二部分：肥胖相关基因 UCP2 在 Barrett 食管粘膜表达变化及临床意义33-44    材料与方法34-35    结果35-41    讨论41-44结论44-45参考文献45-50综述50-60    参考文献55-60附录60-61在读期间发表的文章61-62致谢62

  本文关键词：肥胖相关基因UCP2在Barrett食管粘膜中表达变化及临床意义的研究，由笔耕文化传播整理发布。