慢性阻塞性肺疾病动物模型的研究进展

慢性阻塞性肺疾病(COPD)简称慢阻肺,是一种进行性发展的呼吸系统疾病,严重威胁着人类的健康,给家庭及社会带来了极大的经济负担.然而,目前国内外尚未有统一的研究COPD的动物模型.笔者通过查阅各类与COPD动物模型相关的国内外文献,总结出几种集中常用的COPD动物模型的优势与缺陷,并对其相关检测指标进行归纳,为今后COPD模型的建立提供参考.     

建立慢性阻塞性肺疾病动物模型方法的研究进展

慢性阻塞性肺疾病(COPD)是一种重要的慢性呼吸系统疾病,主要包括慢性支气管炎和肺气肿,患病人数多,病死率高,由于其缓慢进行性发展,严重影响患者的劳动能力和生活质量.为此,国内外许多学者近年来对COPD的发病机制进行了大量的研究工作,但是到目前为止,COPD的研究进展仍然十分缓慢,其主要原因是COPD病因太多,发病机制复杂.本文旨在将国内外有关COPD的实验动物模型进行一次总结,并对各种模型的优缺点给予客观的评价.     

烟熏联合脂多糖制备大鼠慢性阻塞性肺疾病动物模型

目的通过动态观察大鼠慢性阻塞性肺疾病(COPD)动物模型制备过程中肺组织及小支气管的病理改变,以期进一步了解COPD疾病的发展过程。方法采用2次气道内注入细菌内毒素脂多糖和连续被动吸烟4周的方法建立COPD大鼠模型。造模过程中取第7、14、21、28、42天大鼠肺组织进行病理HE染色。结果造模28dCOPD大鼠模型均符合人类COPD的病理形态学特点,模型组大鼠在造模过程中逐渐出现肺气肿表现。结论气道内注入脂多糖与烟熏的复合方法能成功制备较稳定大鼠COPD动物模型。     

慢性阻塞性肺疾病动物模型研究进展

慢性阻塞性肺疾病(COPD)已成为人类健康第三大杀手,迫切需要深入研究揭示其病理分子机制及防治药物。一般COPD分为稳定期及急性加重期COPD(AECOPD),目前在该领域尚未有统一的COPD、AECOPD动物模型造模方法。通过查阅近年来各类与COPD、AECOPD动物模型相关的文献,从单因素诱导方法和复合因素诱导方法两个方面综述几种比较常用的COPD、AECOPD动物模型造模方法,并简述其造模机制、方法及一些优缺点,为COPD动物模型建立和完善提供参考。     

慢性阻塞性肺疾病动物模型研究进展

慢性阻塞性肺疾病(COPD)具有较高发病率及死亡率,给患者及社会带来沉重负担。目前尚没有阻止或逆转COPD疾病进程的有效治疗方法,因此通过动物模型探究其病理过程及新的治疗途径具有重要临床意义。本文对几种常用COPD动物模型及建立方法的研究进展做一总结。     

慢性阻塞性肺部疾病治疗药物的研究动向

慢性阻塞性肺部疾病（COPD）是一组呼吸道气流病理性受限为特征的疾病。包括了慢性气管炎和肺气肿。在过去的10年里．没有新的抗炎药上市用于治疗这种疾病。目前。首要的任务是深入研究COPD的病理过程，以此探索新的动物模型和治疗靶点，研发有潜在治疗作用的新药和治疗方法。文中讨论了正在COPD临床研发中的新抗炎药以及它们的作用机制，同时也提出了一些新的看法。以便进一步理解COPD的病理生理，开发治疗COPD的新药。     

房颤动物模型及其在细胞和分子疗法研究中的应用进展

房颤是多原因引起的心律失常，可导致运输到各器官组织的血量不足，引发血栓、心衰或其他相关的复杂病情。房颤的动物模型分类根据其疾病的症状或诱发因素可分为电生理性模型、神经激素和血管生理失常模型和结构变异模型等。不断涌现的新技术如micro RNA、CRISPR-Cas9体系等为构建房颤疾病动物模型提供了新的技术手段并引导其在疗法研究上的应用新方向。目前房颤治疗方法的研究已经从传统的侵入式电生理方法和抗心律失常药物的使用转向细胞和分子疗法，并在房颤分子机理、靶向治疗和药物筛选等方面都有重要的新进展。本文综述了几类常见的房颤动物模型的构建和特性及其在细胞和分子疗法研究中的应用进展。     

慢性阻塞性肺疾病动物模型建立研究进展

慢性阻塞性肺疾病是一组慢性呼吸系统疾病,严重影响患者的生活质量。建立标准的动物模型,有助于研究COPD的发病机制,有效地指导临床实践。该文对近年来COPD模型的建立进行了系统的回顾,为COPD病因、发病机制和防治等研究奠定基础。     

类风湿性关节炎动物模型应用研究进展

类风湿性关节炎是一种慢性疾病,症状为关节僵硬及发炎、脆弱、丧失可动性、畸形。研究此类疾病的有效方法是建立、研究并应用动物模型。因此,用动物模型研究人类疾病的有效性是动物模型选择的最重要的标准。但不同的动物模型具有不同的特点,应根据实验的要求选择适当的模型。     

慢性阻塞性肺病动物模型的研究进展

慢性阻塞性肺病(COPD)是一种严重的呼吸系统疾病,该病主要包括慢性肺气肿及慢性支气管炎,其发病率、死亡率高,医疗负担重。由于其发病机制、临床发展过程较为复杂,对COPD诊断、治疗的研究工作进展仍然相当缓慢。目前,国内外研究人员通过建立COPD动物模型对该病进行了大量研究工作。旨在对COPD动物模型的建立及评价方法进行总结,并对模型动物选择,评价方法的选择提出一点新的思路。     

Inflammatory airway features and hypothalamic-pituitary- adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal （HPA） axis function in asthmatic rats combined with COPD. Methods Brown Norway （BN） rats were used to model These three models were compared and evaluated with the inflammatory airway diseases of BA, COPD and COPD＋BA. respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness （AHR）, inflammatory cytokines and HPA axis function. Results The inflammatory airway features and HPA axis function in rats in the COPD＋BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group （P 〈0.05）. Conclusions BN rat can be used as an animal model of COPD＋BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.     

Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.     

Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.     

用气道内滴入脂多糖和被动吸烟建立慢性阻塞性肺病大鼠模型

目的建立一种能反映人类慢性阻塞性肺病(COPD)自然发病过程的动物模型.方法通过多次气道内滴入脂多糖(1iPopolysaccharide,LPS)和被动吸烟的方法来制作C0PD大鼠模型,用小动物肺功能仪检测肺功能及对支气管肺泡灌洗液(BALF)、血液细胞进行分类计数.作常规病理检查.结果模型组大鼠各级支气管上皮细胞明显损伤,支气管壁杯状细胞增生(P＜0.01),气道内分泌物增多;气道壁及肺组织有大量炎细胞浸润,气道壁增厚,细支气管伴行肺小动脉管壁亦明显增厚;肺泡过度扩大融合,动态肺顺应性下降,气道阻力明显增大(均P＜0.01);BALF中性粒细胞数量较对照组增多近27倍(P＜0.01),血液中性粒细胞是对照组的近3倍(P＜0.01),且两者呈正相关(r=0.581,P＜0.01).结论通过气道内滴入脂多糖和被动吸烟方式能够建立较符合人类COPD病变的大鼠模型,为进一步研究提供了参照资料.     

COPD相关性肺动脉高压与Rho/Rho激酶信号通路

慢性阻塞性肺疾病（COPD）是一种常见病、多发病,表现为不完全可逆的气流受限。肺动脉高压（PAH）是一组少见的、预后不良的疾病,以增高的肺动脉压力和阻力为特征。慢性缺氧及慢性炎症是COPD相关性PAH的主要发病原因。目前已证实Rho/Rho激酶通路参与PAH的病理生理过程,在PAH的动物模型中阻断该信号通路能够改善疾病的病理改变与预后。     

Flt3L对COPD大鼠铜绿假单胞菌肺炎的防治研究

目的 建立铜绿假单胞菌(PA)肺部感染大鼠慢性阻塞性肺疾病(COPD)模型,研究Flt3L(Fms-like tyrosine kinase-3 ligand )对其炎症反应的防治作用.方法 将50只健康雄性清洁级Wistar大鼠随机分为对照组(NS组)、PA感染对照组(NPA组)、COPD大鼠组(COPD组)、COPD大鼠PA感染组(CPA组)和COPD大鼠PA感染Flt3L处理组(Flt3L组),每组动物各10只.用烟雾暴露法复制大鼠COPD模型,气管内滴入PA溶液复制肺部PA感染模型.COPD组、CPA组、Flt3L组大鼠分别在第1～60天以烟雾暴露法复制COPD模型,Flt3L组于第61～65天连续给予Flt3L(20g/kg)腹腔注射,每天1次,连续5d,第66天同时建立NPA组、CPA组和Flt3L组模型.24h后计算大鼠死亡率,对支气管肺泡灌洗液(BALF)、肺组织进行细菌学、细胞学、病理学等研究.无菌操作下取出大鼠脏器进行细菌培养、菌落计数及细菌鉴定.结果 Flt3L组大鼠存活率(87.5%)显著高于CPA组(50.0%)(P<0.01),Flt3L组大鼠支气管肺泡灌洗液中淋巴细胞数[(0.41～0.05)×109/L]与CPA组[(0.24～0.04)×109/L]比较显著增加(P<0.01),光镜下观察比较发现Flt3L组大鼠肺组织炎症反应较CPA组明显减轻,脏器细菌培养阳性率CPA组(37.5%)显著高于Flt3L组(12.5%)(P<0.01).结论 Flt3L能够增强COPD大鼠对PA肺部感染的抗病力.     

基质金属蛋白酶-9与慢性阻塞性肺疾病的研究

慢性阻塞性肺疾病(COPD)发病机制尚未完全清楚,呼吸道细胞外基质(ECM)重塑,是COPD不可逆性气流受限的重要病理基础。基质金属蛋白酶(MMPs)可降解肺泡壁ECM和基底膜几乎所有的蛋白成分,参与呼吸道重建。本文就MMP-9的来源、基因定位、结构功能、调节机制,近年来临床研究、动物模型研究、基因多态性方面研究的发现简要综述,探讨MMP-9在COPD发病机制中的作用。