Duan Mingke, Fu Yao, Lan Junbin, Wu Yigen, Xu Shengshui, Bai Yukun
Department of Thoracocardiovascular Surgery, Second Municipal Hospital of Xiamen, Academic Hospital of Fujian Traditional Chinese Medicine, Xiamen 361021, China. Email:
Department of Thoracocardiovascular Surgery, Second Municipal Hospital of Xiamen, Academic Hospital of Fujian Traditional Chinese Medicine, Xiamen 361021, China.
Zhonghua Yi Xue Za Zhi. 2014 May 27;94(20):1577-80.
To explore the effects of postconditioning on autophagy of lung injury in situ during lung ischemic reperfusion.
Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups of sham-operated (S), ischemic-reperfusion (I/R) and ischemic postconditioning (IpostC) (n = 8 each). All underwent left thoracotomy after anesthesia. In the S group, a line was only placed around left hilum but not fastened. In the I/R group, a line was fastened to block the blood flow of left lung for 30 min and then loosened for reperfusion for 120 min. In the IpostC group, after blocking the blood flow of left lung for 30 min, left hilum was fastened for 30 sec and loosened for 30 sec. Lung tissues were measured by Western blot. Histopathological changes of lung tissues were observed, lung injury scores calculated and autophagic vacuoles determined by electron microscope.
The relative expression levels of mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) in group I/R (0.40 ± 0.03, 0.33 ± 0.10) were not different with those of group S (0.37 ± 0.07, 0.31 ± 0.10) (both P > 0.05). However, both significantly increased in group IpostC (0.46 ± 0.09, 0.55 ± 0.07) (both P < 0.05). As compared with group S, the relative expression level of LC3-IIand lung injury score significantly increased in groups I/R and IpostC (0.53 ± 0.08, 0.38 ± 0.03 vs 0.25 ± 0.06; 15.79 ± 1.33, 11.67 ± 1.55 vs 5.58 ± 0.39) while obviously declined in group IpostC versus group I/R (all P < 0.05). In group I/R, neutrophil infiltration, interstitial edema, atelectasis and hyaline membrane formation were observed microscopically in lung tissues and the formation of autophagic vacuoles was evident under electron microscope. The changes of group IpostC were milder than those of group I/R.
Ischemic postconditioning has protective effects on lung ischemic reperfusion injury by attenuating autophagy. It may be related with strengthening mTOR.
探讨缺血后处理对肺缺血再灌注原位肺损伤自噬的影响。
将24只雄性Sprague-Dawley大鼠随机分为假手术组(S组)、缺血再灌注组(I/R组)和缺血后处理组(IpostC组),每组8只。所有大鼠麻醉后行左胸切开术。S组仅在左肺门周围放置线但不结扎。I/R组结扎线以阻断左肺血流30分钟,然后松开进行再灌注120分钟。IpostC组阻断左肺血流30分钟后,左肺门结扎30秒,松开30秒。采用蛋白质免疫印迹法检测肺组织。观察肺组织病理变化,计算肺损伤评分,通过电子显微镜检测自噬泡。
I/R组雷帕霉素靶蛋白(mTOR)和磷酸化mTOR(p-mTOR)的相对表达水平(0.40±0.03,0.33±0.10)与S组(0.37±0.07,0.31±0.10)相比差异无统计学意义(P均>0.05)。然而,IpostC组两者均显著升高(0.46±0.09,0.55±0.07)(P均<0.05)。与S组相比,I/R组和IpostC组LC3-II的相对表达水平和肺损伤评分显著升高(0.53±0.08,0.38±0.03比0.25±0.06;15.79±1.33,11.67±1.55比5.58±0.39),而IpostC组与I/R组相比明显下降(P均<0.05)。I/R组肺组织镜下可见中性粒细胞浸润、间质水肿、肺不张和透明膜形成,电镜下可见自噬泡形成。IpostC组的变化比I/R组轻。
缺血后处理通过减弱自噬对肺缺血再灌注损伤具有保护作用。这可能与增强mTOR有关。