本文選題：胃食管反流病 + 內(nèi)臟痛覺高敏感�。� 參考：《第二軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：研究背景： 胃食管反流�。╣astro esophageal reflux disease，GERD)發(fā)病機(jī)制錯(cuò)綜復(fù)雜，，研究顯示部分GERD患者食管的酸暴露正常，有些有過長(zhǎng)時(shí)間的酸暴露時(shí)間，隨著進(jìn)一步的研究，逐漸認(rèn)識(shí)到不能簡(jiǎn)單地將GERD歸結(jié)為反流物對(duì)食管粘膜的化學(xué)性刺激直接造成誘發(fā)組織損傷，使神經(jīng)末梢暴露于酸環(huán)境。目前炎癥和內(nèi)臟高敏感（visceralhypersensitivity,VH）在GERD的發(fā)病過程中起到關(guān)鍵作用。GERD患者食管粘膜中的炎癥介質(zhì)可降低酸敏感離子通道(acid-sensing ion channels,ASICs)受體的信號(hào)轉(zhuǎn)導(dǎo)閾值，從而介導(dǎo)外周致敏，引起酸痛覺高敏現(xiàn)象。ASICs各亞基在哺乳動(dòng)物各器官組織中的分布具有特異性，對(duì)細(xì)胞外pH的敏感性不同。目前明確ASIC1、ASIC2和ASIC3均表達(dá)于食管及其支配神經(jīng)，ASICs的不同亞型可能在GERD的發(fā)病過程中起截然不同的作用。其中ASIC1主要介導(dǎo)對(duì)酸和機(jī)械性刺激的抑制性反應(yīng)，ASIC3主要是介導(dǎo)對(duì)酸刺激和機(jī)械擴(kuò)張刺激的敏感性反應(yīng)，同時(shí)ASIC3還參與酸刺激后的炎癥反應(yīng)過程。但酸敏感離子通道亞基在食管痛覺高敏感形成和維持中機(jī)制未明。 研究目的： 本研究旨在觀察不同ASICs受體亞基在GERD患者食管粘膜的表達(dá)變化并評(píng)估不同ASICs亞基表達(dá)變化與患者食管痛覺閾值改變的相關(guān)性。 研究方法 招募明顯反流、燒心等癥狀的患者填寫GERD調(diào)查問卷。GERD-Q評(píng)分大于6分的患者進(jìn)行電子胃鏡檢查，根據(jù)患者臨床表現(xiàn)(包括臨床癥狀、質(zhì)子泵抑制劑治療反應(yīng)等)、電子內(nèi)鏡和病理檢查結(jié)果，將其分實(shí)驗(yàn)組：反流性食管炎（RE）患者胃鏡下Los-Angeles分級(jí)為B級(jí)及以上的在患處取材（A組）并在患處旁取材（病例自身對(duì)照組-D組）；Los-Angeles分級(jí)為A級(jí)的在患處取材（B組）；對(duì)照組以齒狀線上3cm處為標(biāo)準(zhǔn)，留取受試者食道粘膜活檢標(biāo)本。16位正常志愿者組成無癥狀對(duì)照組（C組）。 使用免疫熒光及實(shí)時(shí)定量聚合酶鏈反應(yīng)（Real-time PCR）的方法檢測(cè)GERD患者食管粘膜ASIC1和ASIC3受體亞基的表達(dá)改變。評(píng)價(jià)GERD患者ASIC1＆3與典型癥狀和炎癥程度的相關(guān)性。 研究結(jié)果 胃鏡下輕度食管炎可見食管粘膜稍紅，嚴(yán)重的可有糜爛和潰瘍。組織學(xué)的改變主要以慢性炎癥為表現(xiàn)，鱗狀上皮增生，粘膜固有層乳頭向上皮腔面延伸，淺層毛細(xì)血管擴(kuò)張。固有層內(nèi)以淋巴細(xì)胞浸潤(rùn)為主，血管化的上皮及其出血的小灶，粘膜下層小靜脈擴(kuò)張，毛細(xì)血管增多。對(duì)照組食管粘膜組織未見明確病理學(xué)改變。 Real Time-PCR檢測(cè)結(jié)果：ASIC1mRNA相對(duì)表達(dá)量為A組36.527±34.912，B組21.242±14.325，C組4.404±2.938，D組5.413±4.215。A組及B組均較C組及D組明顯升高，P＜0.05，A組及B組間與C組及D組間不存在統(tǒng)計(jì)學(xué)差異； ASIC3mRNA相對(duì)表達(dá)量為A組5.200±4.343， B組1.137±0.660，C組0.352±0.164，D組0.419±0.349。A組較B組、C組及D組升高，B組較C組及D組升高，P＜0.05，C組及D組間不存在統(tǒng)計(jì)學(xué)差異。 免疫熒光檢測(cè)結(jié)果：A組ASIC1積分光密度值為0.107±0.012，B組ASIC1積分光密度值為0.100±0.018，C組ASIC1積分光密度值為0.048±0.006，D組ASIC1積分光密度值為0.053±0.007。A組及B組均較C組及D組明顯升高，P＜0.01，A組及B組間與C組及D組間不存在統(tǒng)計(jì)學(xué)差異；A組ASIC3積分光密度值為0.075±0.006， B組ASIC3積分光密度值為0.075±0.004，C組ASIC3積分光密度值為0.055±0.007，D組ASIC3積分光密度值為0.055±0.007。A組及B組均較C組及D組明顯升高，P＜0.01，A組及B組間與C組及D組間不存在統(tǒng)計(jì)學(xué)差異。ASIC1＆3的表達(dá)與RE的炎癥程度無明顯相關(guān)性，ASIC1＆ASIC3與典型癥狀燒心呈正相關(guān)，Pearson相關(guān)系數(shù)分別為0.675、0.571，ASIC1＆ASIC3與典型癥狀胸痛呈正相關(guān)，Pearson相關(guān)系數(shù)分別為0.636、0.611，與反流無明顯相關(guān)性。 結(jié)論 GERD患者食管粘膜ASIC1和ASIC3的表達(dá)發(fā)生了改變，這表明ASIC1和ASIC3在食管痛覺高敏感形成和維持中發(fā)揮重要作用。
[Abstract]:Research background:
The pathogenesis of gastro esophageal reflux disease (GERD) is complicated. The study shows that the acid exposure of the esophagus is normal in some GERD patients and the time of acid exposure for long time. With further study, it is gradually realized that the chemical stimulation of the esophagus mucous membrane can not be simply combined with GERD as a reflux. At present, inflammation and visceral Gao Mingan (visceralhypersensitivity, VH) play a key role in the pathogenesis of GERD, and the inflammatory mediators in the esophageal mucosa of.GERD patients can reduce the signal transduction threshold of the acid sensitive ion channel (acid-sensing ion channels, ASICs) receptor, and thus mediate the signal transduction threshold of the acid sensitive ion channel (acid-sensing ion channels, ASICs). The sensitivity of the.ASICs subunits in the organs and tissues of the mammalian organs is specific, and the sensitivity to the extracellular pH is different. At present, it is clear that ASIC1, ASIC2 and ASIC3 are all expressed in the esophagus and its dominant nerve, and the different subtypes of ASICs may play a very different role in the pathogenesis of GERD. ASIC1 mainly mediates inhibitory reactions to acid and mechanical stimuli, and ASIC3 is mainly mediated by sensitive reactions to acid stimulation and mechanical dilatation, and ASIC3 is also involved in the process of inflammatory response after acid stimulation.
The purpose of the study is:
The purpose of this study was to observe the changes in the expression of different ASICs receptor subunits in the esophageal mucosa of patients with GERD and to evaluate the correlation between the changes in the expression of different ASICs subunits and the changes of the esophageal pain threshold.
research method
Patients who recruited obvious reflux, heart burning and other symptoms filled in the GERD questionnaire.GERD-Q score greater than 6 for electronic gastroscopy, according to the clinical manifestations of the patients (including clinical symptoms, proton pump inhibitors treatment, etc.), electronic endoscopy and pathological results, and the experimental group: reflux esophagitis (RE) patients under the gastroscope Los-An Geles was classified as grade B and above in the affected area (group A) and taken from the affected part (case control group -D); Los-Angeles was classified as class A in the affected area (group B); the control group took 3cm at the dentate line as the standard, and the normal volunteers of.16 position of the esophagus mucosa biopsy specimen of the subjects were composed of the asymptomatic control group (C group).
The expression of ASIC1 and ASIC3 receptor subunits in the esophageal mucosa of GERD patients was detected by immunofluorescence and real-time quantitative polymerase chain reaction (Real-time PCR). The correlation between the atic 1 & 3 and the typical symptoms and the degree of inflammation in the GERD patients was evaluated.
Research results
Mild esophagitis under gastroscope shows a slight reddish mucous membrane of the esophagus, severe erosion and ulcers. The histological changes are mainly characterized by chronic inflammation, squamous epithelium hyperplasia, the extension of the lamina propria papillae to the epithelial cavity, and the dilatation of the superficial capillaries. There was no obvious pathological changes in the esophageal mucosa of the control group.
The results of Real Time-PCR detection: the relative expression of ASIC1mRNA was 36.527 + 34.912 in group A, 21.242 in group B and 4.404 in C in group C, and in group 5.413 + 4.215.A and B group of D group was significantly higher than that in C group and D group, and P < 0.05. Group 0.352 + 0.164, group D 0.419 + 0.349.A group was higher than group B, group C and D group, B group was higher than C group and D group, P < 0.05, C group and D group had no statistical difference.
The results of immunofluorescence detection: A group ASIC1 integral light density value is 0.107 + 0.012, B group ASIC1 integral light density value is 0.100 + 0.018, C group ASIC1 integral light density value is 0.048 + 0.006, D group ASIC1 integral light density value is 0.053 + 0.007.A group and B group is higher than C group and D group, < 0.01. The optical density of ASIC3 integral in A group was 0.075 + 0.006, B group ASIC3 integral light density value was 0.075 + 0.004, C group ASIC3 integral light density value was 0.055 + 0.007, ASIC3 integral light density value of D group was 0.055 + 0.007.A group and B group was significantly higher than C group and D group. There was no significant correlation between the expression of RE and the degree of inflammation of the typical symptoms. The correlation coefficient of Pearson was 0.675,0.571, and the atic 1 & AC 3 was positively correlated with the typical symptoms of chest pain, and the correlation coefficient of Pearson was 0.636,0.611, and there was no obvious correlation with reflux.
conclusion
The expression of ASIC1 and ASIC3 in esophageal mucosa of GERD patients has changed. This indicates that ASIC1 and ASIC3 play an important role in the formation and maintenance of esophageal hyperalgesia.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R571

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本文編號(hào)：2000707