摘要
目的探讨线粒体ATP敏感钾通道开放剂二氮嗪（DE）对肺缺血-再灌注损伤（L／R）的保护作用。方法建立大鼠肺I／R模型，随机设立假手术（sham）组、I／R组、DE组、线粒体ATP敏感钾通道阻断剂5-羟基葵酸（5-HD）组，每组10只，观察各组肺组织病理形态学变化，测定肺湿／干质量比，检测肺组织髓过氧化物酶（MPO）活性、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。结果与sham组比较，I／R组肺组织出现明显损伤性病理形态学变化，肺湿／干质量比明显增加（P〈0．05），肺组织MPO活性显著增高、MDA含量显著增加和SOD活性显著降低（P〈0．05）。与I／R组比较，DE组肺组织损伤明显减轻，肺湿／干质量比降低（P〈0．05），肺组织MPO活性降低、MDA含量减少、SOD活性增高（P〈0．05）。5-HD组各观察指标与I／R组差异无统计学意义（P〉0．05）。结论线粒体ATP敏感钾通道开放剂DE可通过抑制中性粒细胞聚集、减少自由基产生、增强抗氧化能力对大鼠肺缺血-再灌注损伤产生明显保护作用，该保护作用可被线粒体ATP敏感钾通道阻断剂5-HD所拮抗。
Objective To investigate the protective effects of opening of mitochondrial ATP sensitive potassium channel on pulmonary ischemia - reperfusion injury in rat. Methods Forty rats were randomly divided into four groups （ n = 10, respectively）, i.e. group 1 （ sham operation）, group 2 （pulmonary I/R）, group 3 （ DE pretreatment） and group 4 （5 - HD ＋ DE pretreatment）. Pulmonary ischemia - reperfusion injury rat model was established by 45 min of left hilar ligation followed by 120 min of reperfusion. Preconditioning was conducted by pretreatment with mitochondrial ATP sensitive potassium channel opener diazoxide （ DE, 10 mg/kg body weight intraperitoneal injection） 30 min before ischemia. Mitochondrial ATP sensitive potassium channel blocker 5 - hydroxydecanoate （5 - HD, 10 mg/kg body weight） was intravenously injected 15 min before DE pretreatment. Morphological changes of lung tissue were detected by HE staining. The wet - to - dry weight ratio of lung tissue was calculated. The content of malondialdehyde （MDA）, activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） in lung tissue were detected with colorimetric assay. Results Compared with I/R group, congestion and edema of lung tissue in DE pretreatment group was remarkably ameliorated, and the wet - to - dry weight ratio decreased （ P 〈 0. 05 ）, MPO acivity in lung tissue decreased （ P 〈 0. 05 ）, content of MDA reduced （ P 〈 0. 05 ）, SOD activity enhanced （ P 〈 0.05 ）. These DE preconditioning induced- protective effects were blocked by 5 - HD pretreatment. Conclusion The opening of mitochondrial ATP sensitive potassium channel could protect effectively pulmonary ischemia - reperfusion injury in vivo via inhibiting neutrophil recruitment and reducing ROS production, as well as enhancing antioxidation capacity.
出处
《中国急救医学》
CAS
CSCD
北大核心
2010年第3期242-245,F0003,共5页
Chinese Journal of Critical Care Medicine
基金
贵州省优秀科技教育人才省长专项基金资助项目（黔科教办（2003）04号）
关键词
肺
缺血-再灌注损伤
线粒体ATP敏感性钾通道
氧化应激
大鼠
Lung
Ischemia- reperfusion injury
Mitochondrial ATP sensitive potassiumchannel
Oxidative stress
Rat
