中文摘要：

目的评价右美托咪定对大鼠呼吸机相关性肺损伤时γ-氨基丁酸A型受体（GABA。受体）表达的影响。方法清洁级健康成年雄性SD大鼠30只，体重280～320g。采用随机数字表法分为3组（n=10）：对照组（C组）、呼吸机相关性肺损伤组（VILI组）和右美托咪定组（Dex组）。采用潮气量40ml／kg机械通气4h的方法制备大鼠呼吸机相关性肺损伤模型。Dex组麻醉大鼠后腹腔注射右美托咪定50μg／kg，C组和VILI组给予等容量生理盐水。于机械通气4h时处死大鼠取肺组织，观察肺组织病理学结果并行肺损伤评分，收集支气管肺泡灌洗液（BALF），测定总蛋白、IL-18、IL-6及TNF—α的浓度；取肺组织称重，计算肺湿干重（W／D）比值与肺水清除率，检测GABA。受体、IL-1β、IL-6和TNF—d的mRNA表达。结果与c组比较，VILI组和Dex组肺W／D比值、肺损伤评分、BALF总蛋白、IL-1β、IL-6及TNF—α、肺组织IL-1β、IL-6和TNF—α的mRNA表达水平升高，GABA受体表达水平与肺水清除率降低（P〈0．05）；与VILI组比较，Dex组肺W／D比值、肺损伤评分、BALF总蛋白、IL-1β、IL-6及TNF—α、肺组织IL-1p、IL-6和TNF—α的mRNA表达水平降低，GABA。受体表达水平与肺水清除率升高（P〈0．05）。结论右美托咪定减轻大鼠呼吸机相关性肺损伤的机制与上调GABA。受体表达，抑制炎性反应有关。

英文摘要：

Objective To evaluate the effect of dexmedetomidine on the expression of gamma-ami- nobutyric acid （GABAA ） receptors during ventilator-induced lung injury （VILI） in rats. Methods Thirty pathogen-free adult male Sprague-Dawley rats, weighing 280-320 g, were divided into 3 groups （n= 10 each） using a random number table： control group （group C） , group VILI and dexmedetomidine group （group Dex）. The rats were mechanically ventilated for 4 h with the tidal volume of 40 ml/kg to establish VILI model. Dexmedetomidine 50 ~g/kg was injected intraperitoneally after the rats were anesthetized in group Dex, while the equal volume of normal saline was given instead in C and VILI groups. The animals were sacrificed at 4 h of mechanical ventilation, the lungs were removed for examination of patho- logical changes which were scored, bronchoalveolar lavage fluid （BALF） was collected for determination of concentrations of total protein, interleukin-1 beta （IL-1β）, IL-6 and tumor necrosis factor-alpha （TNF-α）, and the lung specimens were obtained for determination of the wet/dry weight ratio （W/D rati- o） , alveolar fluid clearance （AFC） and expression of GABAA receptors, IL-1β, IL-6 and TNF-α mRNA in lung tissues. Results Compared with group C, the W/D ratio, pathological scores, expression of total protein, IL-1β, IL-6 and TNF-α in BALF and expression of IL-1β, IL-6 and TNF-α mRNA in lung tis- sues were significantly increased, and the GABAA receptor expression and AFC were decreased in VILI and Dex groups （P〈O. 05）. Compared with group VILI, the W/D ratio, pathological scores, expression of total protein, IL-1β, IL-6 and TNF-α in BALF and expression of IL-1β, 1L-6 and TNF-α mRNA in lung tissues were significantly decreased, and the GABAA receptor expression and AFC were increased in group Dex （P〈0.05）. Conclusion The mechanism by which dexmedetomidine reduces VILI is related to upregulation of GABAA receptor expression in rats.