右美托咪定对大鼠肺缺血再灌注时脑信号素7A表达的影响

Effect of dexmedetomidine on expression of Semaphorin 7A during lung ischemia-reperfusion in rats

目的评价右美托咪定对大鼠肺缺血再灌注时脑信号素7A表达的影响。方法健康清洁级成年雄性SD大鼠30只,8~12周龄,体重200~240g,采用随机数字表法分为3组(n=10):假手术组(S组)、肺缺血再灌注组(I/R组)和右美托咪定组(D组)。S组仅开胸不阻断左肺门;I/R组采用阻断左侧肺门45min,再灌注120min的方法制备大鼠肺缺血再灌注损伤模型;D组于缺血前30min腹腔注射右美托咪定50μg/kg,然后制备大鼠肺缺血再灌注损伤模型。于再灌注120min时取左肺组织,计算湿重/干重(W/D)比值;采用HE染色法观察肺组织病理学结果,并行肺损伤评分;分别采用Westernblot法和RT-PCR法检测缺血区肺组织脑信号素7A及其mRNA的表达水平;采用ELISA法测定肺组织TNF-α和IL-1β的含量。结果与S组比较,I/R组和D组肺组织W/D比值、肺损伤评分均升高,脑信号素7A及其mRNA表达均上调,TNF-α和IL-1β含量均升高(P<0.05);与I/R组比较,D组肺组织W/D比值和肺损伤评分降低,脑信号素7A及其mRNA表达下调,TNF-α和IL-1β含量降低(P<0.05)。结论右美托咪定减轻大鼠肺缺血再灌注损伤的机制可能与下调肺组织脑信号素7A的表达,从而抑制炎症反应有关。

Objective To evaluate the effect of dexmedetomidine on the expression of Semaphorin 7A during lung ischemia-reperfusion(I/R)in rats. Methods Thirty healthy clean-grade adult male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-240 g, were divided into 3 groups (n=10 each) using a random number table method: sham operation group (S group), I/R group and dexmedetomidine group (D group). Only sternotomy was performed, and the left hilum of lung was not clamped in S group.The model of lung I/R injury was established by clamping the left hilum of lung for 45 min followed by 120 min of reperfusion in I/R group.Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before ischemia, and then the model was established in D group.The rats were sacrificed at the end of reperfusion, and the lungs were removed for examination of the pathological changes(using haematoxylin and eosin staining)which were scored and for determination of the wet to dry weight ratio (W/D ratio), expression of Semaphorin 7A protein and mRNA (by Western blot or real-time polymerase chain reaction), and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in lung tissues (by enzyme-linked immunosorbent assay). Results Compared with S group, W/D ratio and pathological scores were significantly increased, the expression of Semaphorin 7A protein and mRNA was up-regulated, and the contents of TNF-α and IL-1β were increased in I/R and D groups (P<0.05). Compared with I/R group, W/D ratio and pathological scores were significantly decreased, the expression of Semaphorin 7A protein and mRNA was down-regulated, and the contents of TNF-α and IL-1β were decreased in D group (P<0.05). Conclusion The mechanism by which dexmedetomidine reduces lung I/R injury may be related to down-regulating Semaphorin 7A expression, thus inhibiting inflammatory responses of rats.