右美托咪定对大鼠肺移植后肺缺血再灌注损伤的影响

Effect of dexmedetomidine on lung ischemia-reperfusion in rats after lung transplantation

目的评价右美托咪定（DEX）对大鼠肺移植后肺缺血再灌注损伤（LIRI）的影响。方法无特殊病原体（SPF）级雄性Sprague-Dawley大鼠30只，体重250-350g，2～3个月龄，采用随机数字表法，将其分入假手术组、肺移植组和DEX组，每组10只。假手术组，开胸游离左肺门，未行肺移植；肺移植组，左肺移植后开放再灌注2h；DEX组，于移植肺再灌注前30min予大鼠腹腔内注射DEX25μg／kg。再灌注2h后取移植肺组织，测定IL-1β、IL-10、TNF-α水平和髓过氧化物酶（MPO）、丙二醛（MDA）含量；于光学显微镜（×200）下观察肺组织病理学改变。结果肺移植组和DEX组的IL-1β、IL-10、TNF-α水平和MDA、MPO含量均显著高于假手术组（P值均〈0．05）；DEX组的IL-1β、TNF-α水平和MDA、MPO含量均显著低于肺移植组（P值均〈0．05），IL-10水平显著高于肺移植组（P〈0．05）。与肺移植组比较，DEX组肺组织病理学损伤明显减轻，可见少量炎性细胞浸润，肺泡结构较清晰。结论DEX可减轻大鼠肺移植后的LIRI，其机制可能与抑制炎性反应和氧化应激有关。

Objective To evaluate the effect of dexmedetomidine on lung ischemia reperfusion injury （LIRI） after lung transplantation in rats. Methods Thirty pathogen-free male Sprague-Dawley rats, weighing 250-350 g, aged 2-3 months, were divided into 3 groups according to random number table （n = 10 each）： sham operation group （group S）, lung transplantation group （group L） and dexmedetomidine group （group D）. The donor lungs were removed from live donor rats and placed in low potassium dextran solution at 4 ℃. After orthotopic left lung transplantation, the transplanted lung was reperfused for 2 h. in group D, dexmedetomidine 25 μg/kg was injected intraperitoneally 30 min before reperfusion. Lung tissues were collected after reperfusion for 2 h for microscopic examination and determination of Interleukin （IL）-1β, IL-10, tumor necrosis factor （TNF）-α, malondialdehyde （MDA） and myeloperoxidase （MPO） levels. Results Compared with group S, IL-1β, IL-10, TNF-α, MDA and MPO were significantly increased in group L and group D （all P〈0.05）. Compared with group L, IL-1β, TNF-α, MDA and MPO were significantly decreased, while IL-10 was significantly increased in group D （all P〈0.05）. It was found that the pathological changes of lungs were significantly attenuated in group D as compared with group L under optical microscope, and only slight inflammatory cell infiltration and clear stucture of alveoli were seen. Conclusion Dexmedetomidine can attenuate LIRI in a rat model of lung transplantation, which may be related to inhibiton of inflammatory responses and oxidative stress. （Shanghai Med J, 2016, 39 ： 112-115）