关键词:

盐酸纳美芬, 迷走神经电刺激, 肺缺血?再灌注损伤, 强啡肽, 白细胞介素?17

Abstract:

Objective To study the effect and mechanism of namefen hydrochloride combined with electri⁃ cal vagal stimulation on lung ischemia⁃reperfusion injury. Methods A total of 75 rats were randomly divided into model group，electrical vagal stimulation group，nalmefene group，nalmefene combined with electrical vagal stimu⁃ lation group and sham operation group equally（n = 15）. The lung ischemia⁃reperfusion model was established by occlusion of the left pulmonary hilum in the model group. When the lung tissue expanded and the color recovered based on lung ischemia⁃reperfusion model，left vagus nerve was stimulated and namefen（15 μg/kg）was injected into the tail vein immediately in electrical vagal stimulation group and in the namefen group respectively. When the lung tissue expanded and the color recovered based on lung ischemia⁃reperfusion model，left vagus nerve stimula⁃ tion and namefen（15 μg/kg）injected into the tail vein were synchronously applied in nalmefene combined with electrical vagal stimulation group. The sham operation group without occlusion of the left pulmonary hilum was not given any treatment. At 3 h after reperfusion，all rats were detected arterial blood gas value and then sacrificed. The specimens from the upper lobe of the left lung tissue were preserved to observe pulmonary lesions ，detect the ratio of wet/dry weight and the expressions of myeloperoxidase，dynorphin，κ ⁃receptor and IL⁃17 in lung tissue. Results Compared with those in the model group，the value of pCO2，the degree of pulmonary lesions，the ratio of wet/dry weight and the expressions of myeloperoxidase and IL⁃17 in lung tissue were significantly decreased（P < 0.01），and the value of pO2 was significantly increased（P < 0.01）in the electrical vagal stimulation group and the nalmefene group. The expression of dynorphin and κ⁃receptor in lung tissue were significantly decreased in the nalmefene group（P < 0.01），but this expression was not significantly changed in the electrical vagal stimulation group（P > 0.05）. Compared with those in electrical vagal stimulation group，the value of pCO2，pO2，the degree of pulmonary lesions，the ratio of wet / dry weight and the expressions of myeloperoxidase and IL ⁃ 17 in lung tissue were not significantly changed（P > 0.05），but the expression of dynorphin and κ ⁃receptor were significantly decreased in the nalmefene group（P < 0.01）. Compared with those in the nalmefene group or the electrical vagal stimulation group，the value of pCO2，the degree of pulmonary lesions，the ratio of wet/dry weight and the expres⁃ sions of myeloperoxidase，dynorphin，κ⁃receptor and and IL⁃17 in lung tissue were significantly decreased（P < 0.01），and the value of pO2 was significantly increased in the nalmefene combined with electrical vagal stimulation group（P < 0.01）. Conclusion Nalmefene may inhibit the lung ischemia ⁃ reperfusion injury by accelerating the degradation of dynorphin and alleviating the inflammatory reaction of lung tissue. Electric stimulation of vagus nerve attenuates pulmonary ischemia⁃reperfusion injury by inhibiting inflammatory response. The treatment of nalmefene combined with electrical vagal stimulation in the prevention and treatment of lung ischemia⁃reperfusion injury may produce synergistic effects.

Key words:

nalmefene hydrochloride, electrical vagal stimulation, lung ischemia?reperfusion injury, dynorphin, IL?17