目的 研究盐酸右旋美托咪啶对呼吸机所致肺损伤大鼠肺部炎症损伤和细胞外信号调控蛋白激酶磷酸化的影响.方法 36只SPF级雄性SD大鼠随机均分成3组:常规潮气量通气组(C组,8 ml/kg,呼吸频率90次/min).大潮气量通气组(H组,20 ml/kg,呼吸频率50 次/min),大潮气量通气盐酸右旋美托咪啶处理组(D组,20 ml/kg,呼吸频率50 次/min),每组12只.各组通气时间均为4 h,呼吸末气道压力均为0.D组大鼠在机械通气的同时接受盐酸右旋美托咪啶溶液静脉泵入,泵入速度为0.5μg/(kg.h).实验结束处死大鼠,收集支气管肺泡灌洗液和肺组织标本,光镜观察肺病理改变,ELISA法检测BALF中肿瘤坏死因子α,Western blotting检测各组肺组织中ERK1/2、磷酸化ERK1/2(p-ERK1/2)水平.结果 与C组相比,H组和D组肺部有明显病理改变,且干湿重比、总蛋白、白细胞计数、髓过氧化物酶、TNF-α和P-ERK1/2等指标均显著高于C组.与H组相比,D组肺部病理改变明显减轻,ERK1/2磷酸化水平和其他各项指标均显著降低.结论 盐酸右旋美托咪啶静脉输注能显著减轻呼吸机所造成的肺损伤,减少肺部炎症因子的产生,并抑制ERK1/2激活.%Objective To investigate the effect of dexmedetomidine hydrochloride on inflammatory lung injury and phosphorylation of extracellular regulated protein (ERK1/2) in a rat model of ventilator-induced lung injury (VILI). Methods Thirty-six adult male SD rats were randomized into 3 groups (n=12) to receive a 4-h standard ventilation (group C, with tidal volume of 8 ml/kg and respiratory rate of 90/min), high-tidal volume ventilation (group H, with tidal volume of 20 ml/kg and respiratory rate of 50 /min), and high-tidal volume ventilation plus 0.5 μg·Kg-1·H-1 dexmedetomidine infusion (group D), with the maintenance of a positive end expiratory pressure (PEEP) of 0 cmH2O. After mechanical ventilation the rats were sacrificed to collect the lung lavage liquid and lung tissue to examine the pulmonary inflammatory changes and tumor necrosis factor-a (TNF-α) expression as well as the expressions of ERK1/ 2 and p-ERKl/2. Results Groups H and D showed obvious lung injury and significant elevations of the total protein, WBC, MPO, TNF-a, and ERK1/2 phosphorylation as compared with those of group C. The rats in group D showed milder lung pathologies with significantly lower levels of phosphorylation of ERK1/2 and TNF-α compared with those in group H. Conclusion Dexmedetomidine can significantly attenuate VILI, decrease the production of the inflammatory molecules, and inhibit the activation of ERK1/2, demonstrating a protective effect against VILI.
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