PI3K/Akt/HIF-1α信号通路在右美托咪定减轻大鼠肺缺血再灌注损伤中的作用

目的：评价磷脂酰肌醇3-激酶-丝氨酸-苏氨酸蛋白激酶-缺氧诱导因子-1α（phosphatidylinositol 3-kinase-protein-serine-threonine kinases-hypoxia inducible factor-1α，PI3K-Akt-HIF-1α）信号通路在右美托咪定减轻大鼠肺缺血再灌注损伤中的作用。方法：清洁级健康成年雄性SD大鼠32只，体质量250~350 g，采用随机数字表法分为4组（n=8）：假手术组（Sham组）、缺血再灌注组（IR组）、IR+右美托咪定组（D组）、IR+右美托咪定+LY294002组（DL组）。Sham组维持双肺通气3 h，其余组均实施肺IR：左侧肺门夹闭1 h后松开无创血管夹恢复血流再通气2 h。D组泵入10μg·kg^-1右美托咪定负荷量后开始IR模型，DL组泵入0.3 mg·kg^-1 LY294002后泵入右美托咪定，待右美托咪定泵入完毕后开始IR模型。IR模型完毕后肺门离断处死大鼠，留取左肺组织，称重，计算肺湿干重比（W/D）；TUNEL法检测肺组织细胞凋亡情况；4%甲醛固定后HE染色分析肺损伤评分；Western-blot法检测磷酸化Akt（p-Akt）和HIF-1α蛋白表达水平。结果：与Sham组比较，其他3组肺组织W/D升高，肺损伤评分和凋亡指数升高，p-Akt和HIF-1α表达下调（P<0.05）；与IR组比较，D组和DL组肺W/D降低，肺损伤评分和凋亡指数降低，p-Akt和HIF-1α表达上调（P<0.05）；与D组比较，DL组肺W/D升高，肺损伤评分和凋亡指数降低升高，p-Akt和HIF-1α表达下调（P<0.05）。结论：PI3K/Akt/HIF-1α信号通路参与了右美托咪定减轻大鼠肺缺血再灌注损伤的过程。

Effects of PI3K/Akt/HIF-1α signaling pathway in protective effects of dexmedetomidine on lung injury induced by ischemic-reperfusion

OBJECTIVE To evaluate the role of PI3K-Akt-HIF-1α signaling pathway in the protective effects of dexmedetomidine on lung injury induced by ischemic-reperfusion (IR) in rats. METHODS Thirty-two male Sprague-Dawley rats, weighing 250-350 g, were randomly divided into four groups (n=8):sham group (group sham), IR+normal saline grouop (group IR), IR+ dexmedetomidine group (group D), IR+dexmedetomidine + LY294002 group (group DL). Two lung ventilation without IR was maintained for 3h in group sham. IR was established in the other three treatment groups:a 60 min lung ischemia was induced by occluding the hilum of the left lung, followed by a 120 min reperfusion by removing occlusion of the hilum. Rats were sacrificed, left lung was removed, wet lung weight to dry lung weight (W/D) was determined. Pathological changes of lung tissues were analyzed by light microscope. Apoptosis was evaluated by TUNEL methods with AI index. Expression of p-Akt and HIF-1α was determine by Western blot. RESULTS Compared with group sham, W/D, AI and lung injury were increased, p-Akt and HIF-1α were down-regulated in the other three groups. W/D, AI and lung injury were decreased in group D and group DL than in group IR, expression of p-Akt and HIF-1α was up-regulated in group D and group L than in group O. Compared with group D, W/D, AI and lung injury were increased in group DL, expression of p-Akt and HIF-1α was down-regulated in group DL. CONCLUSION The mechanism by which dexmedetomidine reduces lung injury induced by IR may be related to PI3K/Akt/HIF-1α signaling pathway.