缺血后处理对小鼠肠缺血再灌注时肺脏PI3K及Akt表达的影响

Effect of Ischemia Postcondition on Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion and Expression of PI3K and P-Akt in Mice

目的:评价缺血后处理对小鼠肠缺血再灌注时肺脏磷脂酰肌醇3-激酶(PI3K)和丝氨酸-苏氨酸蛋白激酶(Akt)表达的影响。方法:健康雄性C57BL/6J小鼠30只随机分为3组:假手术组(S组)、缺血再灌注组(IR组)、缺血后处理+缺血再灌注组(IPO组)。采用无创动脉夹夹闭肠系膜上动脉根部45min恢复灌注2h的方法制备小鼠肠缺血再灌注损伤模型,IPO组于缺血45min时给予3个循环的灌注30s、缺血30s的处理后恢复灌注。灌注2h采集血样后处死小鼠,留取肺组织,观察肺组织病理学改变并行Smith病理学评分、检测肺组织湿干重比;测定血清MDA含量和SOD活性;检测肺组织PI3K、Akt、p-Akt蛋白的表达情况。结果:与S组比较,IR组MDA含量显著增高,SOD活性显著降低,组织Smith病理学评分和湿干重比显著增高,PI3K及p-Akt蛋白表达上调(P<0.05);与IR组相比,IPO组MDA含量显著下降,SOD活性显著增高,PI3K及p-Akt蛋白表达进一步升高,组织Smith病理学评分和湿干重比降低(P<0.05)。结论:缺血后处理减轻小鼠肠缺血再灌注引起的肺损伤,其机制可能与激活PI3K/Akt信号通路有关。

Objective：To investigate the effect of ischemia postconditioning（IPO）on acute injury induced by intestinal ischemia-reperfusion（IR）and the expression of phosphatidylinositol 3-kinase（PI3K）and protein-serine-threonine kinases（Akt）in mice. Methods：Thirty healthy male C57BL/6Jmice were divided into three groups randomly：Sham operation group（group S）,group IR,and group IPO.Intestinal IR model was produced by occlusion of superior mesenteric artery for 45 min,followed by 2hreperfusion.The mice of IPO group underwent 3cycles of 30 s reperfusion-30 sreocclusion before 2hreperfusion.After 2hof reperfusion,blood and tissues were collected for further analysis.The pathological changes of the pulmonary tissue were observed and evaluated by Smith score.The wet/dry weight ratios of the pulmonary tissue,malondialdehyde（MDA）and superoxide dismutase（SOD）activation in each group were detected.The expression of PI3 K,Akt,phospho-Akt（p-Akt）in pulmonary tissues were also examined.Results：Compared with group S,the pulmonary wet/dry weight ratios,Smith score,the level of serum MDA in groups IRsignificantly increased,SOD activity decreased,and PI3 Kand p-Akt protein expression were up-regulated（P〈0.05）.Compared with group IR,the pulmonary wet/dry weight ratios,Smith score,the level of serum MDA in group IPO significantly decreased,SOD activity was increased,and PI3 K,p-Akt protein expression was up-regulated（P〈0.05）.Conclusion：Ischemia postconditioning can significantly ameliorate the acute lung injury induced by intestinal ischemia reperfusion through promoting the expression of PI3 Kand p-Akt in mice.