南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (08): 980-.doi: 10.12122/j.issn.1673-4254.2019.08.16

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右美托咪定对体外循环缺血再灌注损伤肺组织保护作用的相关信号通路

曹舸，张尔永   

  • 出版日期:2019-08-20 发布日期:2019-08-20

Protective effects of dexmedetomidine against pulmonary ischemia-reperfusion injury during cardiopulmonary bypass in rats

  • Online:2019-08-20 Published:2019-08-20

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摘要： 目的探讨右美托咪定对体外循环缺血再灌注损伤肺组织保护作用可能的信号通路。方法将40只SD成年大鼠随机分 为5组，分别为缺血再灌组（A组）、右美托咪定组（B组）、空白对照组（即假手术组，C组）、渥曼青霉素组（D组）、渥曼青霉素＋右 美托咪定组（E组）。比较5组大鼠的动脉血气指标、肺组织细胞凋亡率、蛋白激酶B（Akt）、磷酸化Akt（p-AKT）、半胱氨酸天冬 氨酸特异性蛋白酶-3（Caspase-3）与caspase-9蛋白表达等情况的差异。结果随着实验时间的延长，A组、B组、D组与E组大鼠 在体外循环前、开放左肺门、实验结束3 个时间点心率、平均动脉压、氧合指数均呈显著的下降趋势，呼吸指数逐渐升高。在 实验结束时，B组大鼠的心率、平均动脉压、氧合指数明显高于其他A组、D组与E组（P<0.05），呼吸指数显著较低（P<0.05）； A~E组大鼠在实验结束时，肺组织病理评分分别为4.89、1.89、0、6.01、5.76；肺组织细胞凋亡率分别为6.25%、3.69%、1.06%、 8.06%、7.79%（P<0.001）；Western blot 检测结果显示，与其他4 组相比，B组大鼠的Akt、p-AKT蛋白表达量显著较高（P<0.05）， caspase-3、caspase-9蛋白相对表达量明显更低（P<0.05）。结论右美托咪定可有效减轻体外循环大鼠的肺损伤，PI3K/Akt信号 通路相关的caspase-3、caspase-9蛋白可能是其作用靶点。

Abstract: Objective To investigate the signaling pathways that mediate the protective effects of dexmedetomidine on lung tissue against ischemia-reperfusion (I/R) injury during cardiopulmonary bypass (CPB). Methods Forty adult SD rats were randomized into 5 groups, namely I/R group (group A), dexmedetomidine group (group B), sham-operated group (group C), oxypenicillin group (group D), and oxypenicillin + dexmedetomidine group (group E). The arterial blood gas, lung tissue apoptosis rate, protein kinase (Akt), phosphorylated Akt (p-AKT), caspase-3 and caspase-9 were compared among the 5 groups. Results In groups A, B, D and E, the heart rate (HR), mean arterial pressure (MAP), and oxygenation index (OI) measured before CPB, at opening of the left hilar and at the end of experiment decreased gradually while the respiratory index (RI) increased at the 3 time points. At the end of experiment, HR, MAP, and OI in group B were significantly higher and RI was significantly lower than those in groups A, D and E (P<0.05). In groups A-E, the pathological scores of the lung tissue at the end of the experiment were 4.89, 1.89, 0, 6.01 and 5.76, respectively, and the cell apoptosis rates in the lung tissue were 6.25%, 3.69%, 1.06%, 8.06% and 7.79%, respectively (P<0.001). Western blotting showed that the expressions of Akt and p-AKT were the highest and those of caspase-3 and caspase-9 were the lowest in group B among the 5 groups (P<0.05). Conclusion Dexmedetomidine can effectively alleviate lung injury in rats during CPB possibly by targeting caspase-3 and caspase-9 proteins that are related to PI3K/Akt signaling pathway.