富马酸氯马斯汀对兔肺缺血再灌注损伤的影响

Effect of clemastine fumarate on lung ischemia-reperfusion injury in rabbits

目的探讨富马酸氯马斯汀对兔肺缺血再灌注损伤的影响。方法健康清洁级新西兰白兔50只，体重2．0—3．0kg，雌雄不拘。采用随机数字表法分为3组：假手术组（Sham组，n=10）、缺血再灌注组（I／R组，n=20）和富马酸氯马斯汀组（Cle组，n=20）。I／R组和Cle组采用夹闭肺门，降低潮气量1h后恢复灌注和通气的方法制备肺缺血再灌注损伤模型，Sham组于通气3h时、I／R组和Cle组分别于再灌注2和4h时，取血样，采用ELISA法检测血清TNF-α和IL-8浓度；行支气管肺泡灌洗，进行支气管肺泡灌洗液白细胞计数；取肺组织测定湿／干重（W／D）比值，RT-PCR法检测肺组织IL-1β和IL-6的mRNA表达，电镜下观察肺组织超微结构，TUNEL法确定细胞凋亡率。结果与Sham组比较，I／R和Cle组肺组织W／D比值、支气管肺泡灌洗液白细胞计数、血清TNF-α和IL-8浓度和肺组织细胞凋亡率升高，肺组织IL-1β和IL-6的mRNA表达上调（P〈0．05或0．01）。与I／R组比较，Cle组肺组织W／D比值、支气管肺泡灌洗液白细胞计数、血清TNF-α和IL-8浓度和肺组织细胞凋亡率降低，肺组织IL-1β和IL-6的mRNA表达下调（P〈0．05或0．01）。Cle组肺组织病理学损伤较I／R组减轻。结论富马酸氯马斯汀可减轻兔肺缺血再灌注损伤。

Objective To investigate the effect of clemastine fumarate on lung ischemia-reperfusion （I/R） injury in rabbits. Methods Fifty New Zealand white rabbits of both sexes, weighing 2.0-3.0 kg, were divided into 3 groups using a random number table： sham operation group （Sham group, n = 10） , I/R group （ n = 20） and clemastine fumarate group （ Cle group, n = 20）. The model of lung I/R was estab- lished by clamping the left hilum of lung and decreasing the tidal volume followed by restoration of perfusion and ventilation 1 h later in I/R and Cle groups. At 3 h of ventilation in group Sham and 2 and 4 h of reperfu- sion in I/R and Cle groups, blood samples were collected for determination of serum tumor necrosis factor- alpha （TNF-α） and interleukin-8 （IL-8） concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and the broncho-alveolar lavage fluid （BALF） was eolleted for determination of white blood cell count. Lung specimens were obtained for microscopic examination of the uhrastructure of lung tis- sues and for determination of wet/dry weight ratio （W/D ratio） , expression of IL-1β and IL-6 mRNA （ by real-time polymerase chain reaction） and cell apoptosis （by TUNEL）. The apoptosis rate was calculated. Results Compared with Sham group, the W/D ratio, white blood cell count in BALF, serum concentra- tions of TNF-α and IL-8 and apoptosis rate were significantly increased, and the expression of IL-1β and IL-6 mRNA was up-regulated in I/R and Cle groups （P〈0.05 or 0. 01 ）. Compared with I/R group, the W/ D ratio, white blood cell count in BALF, serum concentrations of TNF-α and IL-8 and apoptosis rate weresignificantly decreased, and the expression of IL-1β and IL-6 mRNA was down-regulated in Cle group （P〈 0.05 or 0.01 ）. The pathological changes of lung tissues were significantly attenuated in Cle group than in I/ R group. Conclusion Clemastine fumarate can attenuate lung I/R injury in rabbits.