阻断β-catenin信号通路对哮喘气道重塑影响的实验研究

发布时间：2018-05-26 21:19

本文选题：哮喘 + 气道重塑　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:通过采用ICG001阻断β-catenin信号通路,观察阻断β-catenin通路对哮喘气道重塑的影响及相关机制。方法:将40只8周龄SPF级雄性Wistar大鼠,随机分为对照组(A组)、哮喘组(B组)、布地奈德组(C组)、ICG001组(D组),每组10只。采用卵白蛋白(OVA)致敏法,建立哮喘气道重塑模型。A组大鼠每次给予同等剂量的生理盐水。B、C、D组大鼠于d1、d8致敏,d15开始激发,20min/d,共8周;C组于每次激发前2小时雾化吸入布地奈德2mg;D组于每次激发前半小时腹腔注射ICG001 5mg/kg。各组大鼠于末次激发后24小时内收集肺组织标本。大体上观察肺组织标本,光镜下观察HE染色切片,用BI2000分析系统测量支气管壁及平滑肌厚度。实时荧光定量PCR检测肺组织Snail、MMP-7 m RNA的表达。结果:行为学观察,B组大鼠整体毛发杂乱、活动减少、体型消瘦,每次激发后出现不同程度的立毛、尖叫、呼吸急促、口唇紫绀等,C、D组上述表现不明显,A组未出现上述表现。肺组织大体观察,B组肺组织表面不规则,颜色浑浊,呈不均匀性膨胀,可见不规则暗红色充血区,C、D组改变轻微,A组无上述改变。光镜下观察肺组织HE染色切片,A组支气管壁形态结构正常,管腔无狭窄,未见平滑肌增厚及炎细胞浸润,B组支气管管壁及平滑肌明显增厚,管腔变窄,支气管黏膜下有大量炎细胞浸润,C、D组较B组明显改善。测量支气管壁及平滑肌厚度,B组支气管壁、平滑肌厚度[(43.22±1.36)、(21.78±0.84)μm]显著高于A组[(26.32±0.24)、(14.21±0.13)μm];C、D组分别为[(36.51±0.44)、(19.67±0.92)μm]、[(32.69±1.57)、(17.39±0.91)μm],差异有统计学意义(均P0.01)。实时荧光定量PCR检测肺组织Snail、MMP-7表达情况,结果提示Snail、MMP-7的m RNA表达情况B组C组A组D组,差异有统计学意义(均P0.01)。结论:1.ICG001阻断β-catenin信号通路能够逆转哮喘气道重塑。2.ICG001通过阻断β-catenin信号通路抑制下游Snail、MMP-7的表达逆转哮喘气道重塑。
[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 卤0.24 卤0.21 卤0.13 渭 m], [36.51 卤0.4419.67 卤0.92 渭 m], [32.69 卤1.57, 17.39 卤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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R562.25

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