本文選題：兔　切入點(diǎn)：胃食道反流　出處：《復(fù)旦大學(xué)》2014年博士論文　論文類型：學(xué)位論文

【摘要】：第一部分喉咽反流病兔動物模型的建立與評價(jià)目的：建立和評估喉咽反流兔動物模型并利用此模型研究下食道括約肌功能障礙和反回流性喉炎之間的關(guān)系。方法：12只健康新西蘭大白兔(2.5-3.5公斤)分成兩組。8只行下食道括約肌全切除術(shù)以誘導(dǎo)反流。其余的四只行假手術(shù)作為對照組。所有動物術(shù)前行喉鏡檢查和24小時(shí)食管內(nèi)pH值檢測,術(shù)后2周和8周重復(fù)以上檢查,然后處死所有動物,以獲得組織學(xué)的結(jié)果。結(jié)果：下食道括約肌全切除術(shù)使實(shí)驗(yàn)組動物術(shù)后的反流指數(shù)(reflux index, R),最長反流持續(xù)時(shí)間(duration of the longest reflux episode, DLRE)和24小時(shí)內(nèi)總反流次數(shù)顯著增加。實(shí)驗(yàn)組術(shù)前和術(shù)后2周反流喉鏡評分(reflux finding score, RFS)無顯著性差異(P=0.11)。但實(shí)驗(yàn)組術(shù)前和術(shù)后8周RFS由4.6+0.9上升到8.3+3.6,有顯著性差異(P=0.02)。實(shí)驗(yàn)組與對照組相比,粘膜下腺體增生和炎癥反應(yīng)有顯著性差異。結(jié)論：本研究結(jié)果顯示,在兔動物模型中慢性食管下段括約肌功能障礙可導(dǎo)致反流性喉炎。第二部分 喉咽反流病兔動物模型食道及聲帶粘膜細(xì)胞間隙的研究目的：本研究中,我們利用反流動物模型研究了兔喉和食道上皮在透射電鏡下的組織學(xué)變化,從而揭示喉咽反流(laryngopharyngeal reflux, LPR)和胃食管反流(gastroesophageal reflux, GER)的關(guān)系以及擴(kuò)張的細(xì)胞間隙(dilated intercellular space,DIS)可否作為LPR形態(tài)標(biāo)志。方法：8只新西蘭大白兔分為2組。4只兔子行下食道括約肌全切除術(shù)以誘導(dǎo)反流。余下4只行假手術(shù),作為對照組。所有動物術(shù)后12周后處死以獲得組織學(xué)及電鏡結(jié)果。結(jié)果：實(shí)驗(yàn)組和對照組的食道和喉組織學(xué)結(jié)果有顯著性差異(P=0.041和0.014)。與對照組相比,實(shí)驗(yàn)組食道和喉上皮細(xì)胞間隙(intercellular space,IS)有顯著性差異(P0.001)。結(jié)論：本實(shí)驗(yàn)的結(jié)果提示LPR和GER有相似的發(fā)病機(jī)制,而且DIS可作為兔LPR模型的形態(tài)學(xué)指標(biāo)。與對照組相比,實(shí)驗(yàn)組食道和喉上皮細(xì)胞間隙(intercellular space,IS)有顯著性差異(P0.001)。第三部分緊密連接蛋白Claudin-3和Occludin在反流動物模型中的表達(dá)目的：建立和評估喉咽反流大鼠動物模型并利用此模型研究喉內(nèi)claudin-3和occludin表達(dá)和喉咽反流之間的關(guān)系。方法：8只健康大白鼠(250-300 g)分成兩組。4只行下食道括約肌全切除術(shù)以誘導(dǎo)反流。其余的四只行假手術(shù)作為對照組。所有動物術(shù)后12周處死,以獲得組織學(xué)的結(jié)果。應(yīng)用Western blot和免疫熒光檢測食道及喉粘膜樣本中claudin-3和occludin的表達(dá)。結(jié)果：實(shí)驗(yàn)組食道和喉內(nèi)粘膜淋巴細(xì)胞浸潤有顯著增加(P=0.001和0.002)。實(shí)驗(yàn)組食道和喉內(nèi)粘膜claudin-3表達(dá)水平明顯低于對照組(P=0.045,0.037)；occludin表達(dá)無明顯差異。結(jié)論：本實(shí)驗(yàn)結(jié)果提示在喉咽反流大鼠模型中,claudin-3表達(dá)的降低對于反流性喉炎有敏感的指示意義。
[Abstract]:Part I Establishment and evaluation of rabbit model of laryngopharyngeal reflux objective: to establish and evaluate the rabbit model of laryngopharyngeal reflux and to study the relationship between lower esophageal sphincter dysfunction and reflux laryngitis. 12 healthy New Zealand rabbits (2.5-3.5 kg) were divided into two groups: total resection of lower esophagus sphincter was performed to induce reflux in two groups. The other four rabbits underwent sham-operation as control group. All animals underwent laryngoscopy before operation and 24 hours esophageal pH test. Two and eight weeks after the operation, all the animals were killed. Results: total resection of lower esophageal sphincter significantly increased the reflux index (RV), duration of the longest reflux isodee (DLRED) and total reflux times in 24 hours. There was no significant difference in reflux finding score before and 2 weeks after operation in the test group (P < 0.01), but the RFS in the experimental group increased from 4.60.9 to 8.33.6 before and 8 weeks after operation, there was significant difference between the experimental group and the control group. There were significant differences in submucous gland hyperplasia and inflammatory response. Conclusion: the results of this study show that, Chronic lower esophageal sphincter dysfunction may lead to reflux laryngitis in rabbit models. We studied the histological changes of rabbit laryngeal and esophageal epithelium under transmission electron microscope (TEM) using a reflux animal model. To reveal the relationship between laryngopharyngeal reflux (LPRs) and gastroesophageal reflux (GERS), and whether dilated intercellular space DISs can be used as a morphological marker of LPR. Methods eight New Zealand white rabbits were divided into 2 groups with 4 rabbits with lower esophageal sphincter. Total resection to induce reflux. The remaining 4 were sham-operated. All animals were killed 12 weeks after operation to obtain histological and electron microscopic results. Results: there were significant differences in histological results of esophagus and larynx between experimental group and control group. Conclusion: the results of this study suggest that LPR and GER have similar pathogenesis, and DIS can be used as a morphological index of LPR model in rabbits. There was significant difference between the esophageal and laryngeal epithelial cells in the experimental group (P0.001). The third part of the tight junction protein Claudin-3 and Occludin expression in reflux animal model: to establish and evaluate the rat model of larynx reflux and use this model. To study the relationship between the expression of claudin-3 and occludin in larynx and pharynx reflux. Methods eight healthy rats were divided into two groups: total resection of lower esophageal sphincter to induce reflux. The animals were executed 12 weeks after operation. Western blot and immunofluorescence were used to detect the expression of claudin-3 and occludin in esophageal and laryngeal mucosa samples. Results: lymphocyte infiltration in esophagus and larynx of experimental group was significantly increased by P0. 001 and 0. 002. The expression of claudin-3 in the laryngeal mucosa was significantly lower than that in the control group. Conclusion: the decrease of the expression of claudin-3 in laryngopharyngeal reflux rat model has a sensitive indicative significance for reflux laryngitis.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R571;R-332

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本文編號：1592916