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| 右美托咪定对大鼠离体肺缺血-再灌注损伤时ERK 1/2和Akt激活的影响 |
| Effect of dexmedetomidine on activations of pulmonary ERK 1/2 and Akt during isolated lung ischemia-reperfusion injury in rats |
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| DOI：10.12089/jca.2018.04.015 |
| 中文关键词: 右美托咪定 胞外信号调节激酶 丝氨酸/苏氨酸蛋白激酶 缺血-再灌注损伤 |
| 英文关键词: Dexmedetomidine Extracellular signal-regulated kinase Serine-threonine kinase Ischemia-reperfusion injury |
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| 中文摘要: |
| 目的 评价右美托咪定对大鼠离体肺缺血-再灌注损伤(lung ischemia-reperfusion injury,LIRI)时胞外信号调节激酶(ERK 1/2)和丝氨酸/苏氨酸蛋白激酶(Akt)激活的影响。方法 成年雄性SD大鼠45只,随机分为三组:对照组(C组)、缺血-再灌注组(IR组)和右美托咪定组(DEX组),每组15只。C组大鼠离体肺在IL-2离体肺灌流系统内维持正常的生理活动,只通气和灌流150 min;IR组和DEX组大鼠离体肺在IL-2离体肺灌流系统中维持15 min后,停止通气和灌流60 min后再通气和复灌75 min;DEX组复灌开始时于离体灌流液中加入右美托咪定10 nmol/L。C组和IR组分别于灌流75 min和复灌开始时在离体灌流液中加入等体积生理盐水。检测肺泡损伤率（IAR）。采用逆转录-聚合酶链式反应(RT-PCR)法测定肺组织ERK 1/2、Akt mRNA表达量,Western blot法测定磷酸化-ERK (p-ERK 1/2)、磷酸化-Akt (p-Akt)蛋白含量。结果 与C组比较,IR组和DEX组IAR、肺组织ERK 1/2、Akt mRNA表达量和p-ERK 1/2及p-Akt蛋白含量均明显升高(P＜0.05);与IR组比较,DEX组IAR、肺组织ERK 1/2、Akt mRNA表达量和p-ERK1/2及p-Akt蛋白含量均明显降低(P＜0.05)。结论 右美托咪定可减轻大鼠离体LIRI,其机制可能与其抑制ERK 1/2和Akt的激活有关。 |
| 英文摘要: |
| Objective To investigate the effect of dexmedetomidine on activations of pulmonary extracellular signal-regulated kinase 1/2 (ERK 1/2) and serine-threonine kinase (Akt) during isolated lung ischemia-reperfusion injury (LIRI) in rats. Methods Forty-five adult male Sprague-Dawley rats were randomly divided into three groups (n=15 each): control group (group C), ischemia-reperfusion group (group IR) and dexmedetomidine group (group DEX). Isolated rat lungs were maintained for normal physical activity, and only received ventilation and perfusion for 150 min in the IL-2 ex-vivo lung perfusion system in group C. Isolated rat lungs were subjected to 60 min of ischemia and apnea followed by 75 min reperfusion and ventilation 15 min after perfusion in the IL-2 ex-vivo lung perfusion system in groups IR and DEX. Dexmedetomidine with a dose of 10 nmol/L was administrated into perfusion fluid at the onset of reperfusion in group DEX, and the same volume of saline was injected when perfusion for 75 min and at the onset of reperfusion in groups C and IR, respectively. Pathological changes of lungs were examined and the injured alveolus rate (IAR) was counted under light microscope. The expression levels of ERK 1/2 or Akt mRNA and phosphorylate-ERK 1/2 (p-ERK 1/2) or phosphorylate-Akt (p-Akt) protein of lung tissue were tested by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. Results Compared with group C, the IAR and the expression levels of ERK 1/2 and Akt mRNA or p-ERK 1/2 and p-Akt protein in lung tissue were higher in groups IR and DEX (P＜0.05). Compared with group IR, the IAR and the expression levels of ERK 1/2 and Akt mRNA or p-ERK 1/2 and p-Akt protein in lung tissue were lower in group DEX (P＜0.05). Conclusion Dexmedetomidine may reduce LIRI in rat isolated lungs via inhibiting the expressions of IL-6 and IL-8, and the mechanism may be related to suppressing activations of ERK 1/2 and Akt. |
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