本文選題：哮喘 + 氣道重塑��； 參考：《山西醫(yī)科大學》2017年碩士論文

【摘要】：目的:通過采用ICG001阻斷β-catenin信號通路,觀察阻斷β-catenin通路對哮喘氣道重塑的影響及相關(guān)機制。方法:將40只8周齡SPF級雄性Wistar大鼠,隨機分為對照組(A組)、哮喘組(B組)、布地奈德組(C組)、ICG001組(D組),每組10只。采用卵白蛋白(OVA)致敏法,建立哮喘氣道重塑模型。A組大鼠每次給予同等劑量的生理鹽水。B、C、D組大鼠于d1、d8致敏,d15開始激發(fā),20min/d,共8周;C組于每次激發(fā)前2小時霧化吸入布地奈德2mg;D組于每次激發(fā)前半小時腹腔注射ICG001 5mg/kg。各組大鼠于末次激發(fā)后24小時內(nèi)收集肺組織標本。大體上觀察肺組織標本,光鏡下觀察HE染色切片,用BI2000分析系統(tǒng)測量支氣管壁及平滑肌厚度。實時熒光定量PCR檢測肺組織Snail、MMP-7 m RNA的表達。結(jié)果:行為學觀察,B組大鼠整體毛發(fā)雜亂、活動減少、體型消瘦,每次激發(fā)后出現(xiàn)不同程度的立毛、尖叫、呼吸急促、口唇紫紺等,C、D組上述表現(xiàn)不明顯,A組未出現(xiàn)上述表現(xiàn)。肺組織大體觀察,B組肺組織表面不規(guī)則,顏色渾濁,呈不均勻性膨脹,可見不規(guī)則暗紅色充血區(qū),C、D組改變輕微,A組無上述改變。光鏡下觀察肺組織HE染色切片,A組支氣管壁形態(tài)結(jié)構(gòu)正常,管腔無狹窄,未見平滑肌增厚及炎細胞浸潤,B組支氣管管壁及平滑肌明顯增厚,管腔變窄,支氣管黏膜下有大量炎細胞浸潤,C、D組較B組明顯改善。測量支氣管壁及平滑肌厚度,B組支氣管壁、平滑肌厚度[(43.22±1.36)、(21.78±0.84)μm]顯著高于A組[(26.32±0.24)、(14.21±0.13)μm];C、D組分別為[(36.51±0.44)、(19.67±0.92)μm]、[(32.69±1.57)、(17.39±0.91)μm],差異有統(tǒng)計學意義(均P0.01)。實時熒光定量PCR檢測肺組織Snail、MMP-7表達情況,結(jié)果提示Snail、MMP-7的m RNA表達情況B組C組A組D組,差異有統(tǒng)計學意義(均P0.01)。結(jié)論:1.ICG001阻斷β-catenin信號通路能夠逆轉(zhuǎn)哮喘氣道重塑。2.ICG001通過阻斷β-catenin信號通路抑制下游Snail、MMP-7的表達逆轉(zhuǎn)哮喘氣道重塑。
[Abstract]:Aim: to investigate the effect of 尾 -catenin pathway blocking by ICG001 on airway remodeling in asthmatic rats. Methods: forty 8-week-old SPF male Wistar rats were randomly divided into control group (n = 10), asthma group (n = 10) and budesonide group (n = 10). Ovalbumin was sensitized by OVA. The airway remodeling model of asthma was established. Group A rats were given the same dose of normal saline at each time. The rats of group B were sensitized on the 1st day, 8 days, and the rats of group C were stimulated for 20 min / d on the 8th day. The rats in group C were inhaled with budesonide 2 mg / d 2 hours before each shot for a total of 8 weeks, and inhaled budesonide 2 mg / d for each time. ICG001 5 mg / kg was injected intraperitoneally in the first half hour. Lung tissue specimens were collected within 24 hours after the last challenge. Lung tissue specimens were observed and HE stained sections were observed under light microscope. The thickness of bronchial wall and smooth muscle was measured by BI2000 analysis system. The expression of MMP-7 m RNA in lung tissue was detected by real time fluorescence quantitative PCR. Results: the behavior of rats in group B was disorderly, decreased in activity, thin in shape, with different degrees of hair, screaming, shortness of breath, cyanosis of lips, etc. The above findings were not obvious in group A. In group B, the surface of lung tissue was irregular, the color was turbid, and the lung tissue was inhomogeneous swelling. No such changes were found in group A. Under light microscope, the bronchial wall in group A was normal in morphology and structure, no stenosis in lumen, no thickening of smooth muscle and infiltration of inflammatory cells in group A, and obvious thickening of bronchial wall and smooth muscle in group B, and narrowing of lumen in group B. A large number of inflammatory cells infiltrated in submucous membrane of bronchus. The thickness of bronchial wall and smooth muscle in group B was significantly higher than that in group A [26.32 鹵0.24 鹵0.21 鹵0.13 渭 m], [36.51 鹵0.4419.67 鹵0.92 渭 m], [32.69 鹵1.57, 17.39 鹵0.91 渭 m]. Real-time quantitative PCR was used to detect the expression of Snailan MMP-7 in lung tissue. The results showed that the m RNA expression of Snail-MMP 7 in group B was significantly higher than that in group D (P 0.01). Conclusion 1. ICG001 blocking 尾 -catenin signaling pathway can reverse airway remodeling of asthma. 2. ICG001 can reverse airway remodeling by blocking 尾 -catenin signaling pathway to inhibit the expression of Snailan MMP-7 in the lower reaches of asthma.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R562.25

【參考文獻】

相關(guān)期刊論文 前2條

1 蘭靜;李秋根;;實時熒光定量PCR技術(shù)理論研究及其在醫(yī)學方面的應(yīng)用[J];南昌大學學報(醫(yī)學版);2011年10期

2 葉新民;鐘南山;;基質(zhì)金屬蛋白酶與支氣管哮喘氣道重塑[J];中華哮喘雜志(電子版);2009年05期

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本文編號：1938927