本文關鍵詞：肥胖相關基因UCP2在Barrett食管粘膜中表達變化及臨床意義的研究，由筆耕文化傳播整理發(fā)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達變化的研究。2. UCP2蛋白在Barrett食管粘膜中表達與BMI和WC的關系,并探討其臨床意義。方法1.記錄患者一般情況，包括其年齡、性別、病程、癥狀等，其中癥狀包括：反酸或反流、燒心、上腹部不適或疼痛、吞咽困難，消化道外癥狀(如咳嗽，咽部不適包括咽炎、癔球癥等)。并記錄患者的身高、體重和臀圍。2.胃鏡下每位患者分別于四個象限各取活檢一塊，活檢標本分為兩份，一份放入中性福爾馬林中固定，另一份快速放入液氮中保存。3.實驗分為正常對照組、RE組、BE組和EAC組，并根據(jù)BMI的大小分為BMI≥24和BMI<24兩個亞組，根據(jù)WC的大小分為WC≥80/85（女/男）和WC<80/85（女/男）兩個亞組。4.用免疫組織化學方法檢測對照組和病例組食管粘膜中TGF-β、UCP2的表達，黃嘌呤氧化酶法測定SOD活力，硫代巴比妥酸顯色法檢測血漿MDA含量。結果1.正常對照組、RE組、BE組和EAC組血漿MDA含量呈增加趨勢，各組差異有統(tǒng)計學意義（P<0.05）,血漿SOD活力逐漸降低，正常對照組和各病例組差異有統(tǒng)計學意義（P<0.05)，但RE組和BE組以及BE組和EAC組差異沒有統(tǒng)計學意義（P>0.05）。2.各組均表達TGF-β1，按對照組，RE組、BE組和EAC組順序,粘膜上皮中TGF-β1蛋白的表達量逐漸增加，但差異無統(tǒng)計學意義（P>0.05）；正常對照組無UCP2蛋白表達，，RE組、BE組和EAC組UCP2蛋白的表達量逐漸增加，各組差異有統(tǒng)計學意義（P<0.05)。3.對BMI<24和BMI≥24及WC≥80/85（女/男）和WC<80/85（女/男）亞組患者食管粘膜中UCP2表達量進行卡方檢驗。隨BMI增加，UCP2表達降低，但差異無統(tǒng)計學意義（P>0.05）；WC增加，UCP2表達降低，RE組、BE組和病例組差異有統(tǒng)計學意義（P<0.05）;并對患者食管粘膜UCP2的表達和患者BMI、WC的大小進行相關性分析，得出患者WC和UCP2表達的相關系數(shù)r=-0.889，P=0.000,BMI和UCP2表達的r=-0.102, P=0.237，說明WC的大小和UCP2的表達相關性更強。4. BMI的增加，增加了反酸或反流、上腹部不適或疼痛和惡心等胃食管反流病癥狀的發(fā)生率，但BMI≥24較BMI<24的患者上述癥狀出現(xiàn)的頻率差異無統(tǒng)計學意義（P>0.05）；燒心癥狀在兩組間差異有統(tǒng)計學意義（P<0.05）。較WC<80/85(女/男)患者，WC≥80/85(女/男)的患者反酸或反流、燒心、上腹部不適或疼痛等癥狀均增加，且差異有統(tǒng)計學意義（P<0.05）。將GERD細分為RE、BE兩組后，隨著BMI和WC的增加，同樣也增加了患者反酸或反流，燒心，上腹部不適或疼痛和惡心等癥狀的發(fā)生率。但WC的大小較BMI的大小對癥狀的影響更明顯。結論肥胖Barrett食管患者食管粘膜中UCP2表達降低，同時肥胖尤其是腹型肥胖增加了Barrett食管的發(fā)病風險，并使Barrett食管患者的反酸，燒心等癥狀的加重。但是否UCP2表達降低導致肥胖，進而使Barrett食管發(fā)生的風險增加，還有待進一步研究。

    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.

肥胖相關基因UCP2在Barrett食管粘膜中表達變化及臨床意義的研究

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達差異的研究14-33    材料與方法15-24    結果24-31    討論31-33第二部分：肥胖相關基因 UCP2 在 Barrett 食管粘膜表達變化及臨床意義33-44    材料與方法34-35    結果35-41    討論41-44結論44-45參考文獻45-50綜述50-60    參考文獻55-60附錄60-61在讀期間發(fā)表的文章61-62致謝62

  本文關鍵詞：肥胖相關基因UCP2在Barrett食管粘膜中表達變化及臨床意義的研究，由筆耕文化傳播整理發(fā)布。