摘要
目的研究慢性阻塞性肺疾病(COPD)大鼠Ⅱ型肺泡上皮细胞(AECⅡ)凋亡水平的变化,探讨AECⅡ凋亡在COPD发病机制中的作用及吸入糖皮质激素的影响。方法气管内注入脂多糖联合香烟烟熏法建立COPD动物模型,雾化吸入布地奈德(BUD)混悬液进行干预。将48只大鼠随机分为8组:空白对照组、BUD对照组、COPD15d组、低剂量BUD干预15d组、高剂量BUD干预15d组、COPD30d组、低剂量BUD干预30d组、高剂量BUD干预30d组。各组大鼠分别于第15或30d处死。肺组织切片用HE染色观察肺泡破坏程度,用免疫组化法和TUNEL法观察AECⅡ凋亡情况。结果(1)不同时点COPD组大鼠肺泡结构破坏程度、AECⅡ凋亡水平显著高于空白对照组和BUD对照组(P均<0.01),且呈时间依赖性趋势;AECⅡ凋亡水平和肺泡结构破坏程度之间呈显著正相关(免疫组化法:r=0.92,P<0.01;TUNEL法:r=0.90,P<0.01)。(2)BUD可显著降低肺泡结构破坏程度(P<0.01)及AECⅡ凋亡水平(P<0.01),且呈剂量依赖性趋势。结论AECⅡ凋亡可能通过参与肺泡结构破坏的方式参与了COPD的形成。吸入性糖皮质激素可显著降低肺泡破坏程度和AECⅡ凋亡水平,为其用于COPD的治疗提供了实验依据。
Objective To investigate the apoptosis of type Ⅱ alveolar epithelial cells（AECⅡ ） in rat model of chronic obstructive puhnonary disease （COPD） and observe the effects of inhaled glucocorticoid on AEC Ⅱ apoptosis. Methods A rat model of COPD was established by tobacco smoke inhalation and intratracheally administered hpopolysaccharide. Forty-eight rats were randomly divided into eight groups, ie. a sam control group, a budesonide （BUD） control group, a 15-days group of COPD, a 15-days group with low dose BUD,a 15-days group with high dose BUD,a 30-days group of COPD, a 30-days group with low dose BUD and a 30-days group with high close BUD. The rats were sacrificed on 15th and 30th day respectively to obtain the pulmonary tissue. The degree of alveolar destruction was observed by HE stain and the apoptosis of AEC Ⅱ was detected by immunohistochemistry and TUNEL methods. Results The degree of alveolar destruction and the apoptosis of AECⅡ were significantly increased in COPD rats in a time-dependent manner than those in the BUD and sam control groups （ both P 〈 0.01 ） with a significantly positive correlation between each other （ P 〈 0.01 ）,Inhaled glucocorticoid Could decrease the degree of alveolar destruction （ P 〈 0.01 ） and the apoptosis of AECⅡ in COPD rats significantly（ P 〈 0.01 ） in a dose-dependent manner. Conclusion The apoptosis of AECⅡ may be involved in the pathological process of COPD through alveolar destruction, and inhaled glucocorticoid can prevent alveolar destruction and the apoptosis of AEC Ⅱ in COPD rats, which provide futher evidence for inhaled glucoeorticoid in COPD treatment.
出处
《中国呼吸与危重监护杂志》
CAS
2007年第5期381-384,377,I0003,共6页
Chinese Journal of Respiratory and Critical Care Medicine
