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| 七氟醚介导腺苷A3受体通路减轻大鼠机械通气肺损伤 |
| Sevoflurane mediated A3 adenosine receptor pathway reduces ventilator induced lung injury in rats |
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| DOI：10.12089/jca.2018.09.014 |
| 中文关键词: 机械通气肺损伤 七氟醚 腺苷3受体 |
| 英文关键词: Ventilator induced lung injury Sevoflurane A3 adenosine receptor |
| 基金项目: |
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| 摘要点击次数: 3034 |
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| 中文摘要: |
目的 探讨腺苷A3受体(A3AR)在七氟醚减轻大鼠机械通气肺损伤(VILI)中的作用及其机制。
方法 SPF级健康雄性成年大鼠40只, 体重200～250 g, 随机分为五组:假通气组(Sham组), 模型对照组(CON组), 七氟醚处理组(SEV组), 七氟醚联合A3AR抑制剂处理组(SM组), A3AR抑制剂处理组(MRS组), 每组8只。除Sham组不进行通气外, 其他四组均在麻醉气管插管后行机械通气(VT 12 ml/kg), 持续正压通气6 h, 建立大鼠VILI模型。Sham组: 氯胺酮麻醉后直接处死;CON组: 氯胺酮维持麻醉状态;SEV组: 2％七氟醚维持麻醉;SM组: 机械通气开始前30 min腹腔注射MRS-1191 1 mg/kg, 2％七氟醚维持麻醉;MRS组: 机械通气开始前30 min腹腔注射MRS-1191 1 mg/kg, 氯胺酮维持麻醉。实验结束后处死大鼠, 收集支气管肺泡灌洗液(BALF)和肺组织标本。采用Western blot法检测肺组织A3AR、gp91phox蛋白含量。检测BALF中炎性因子TNF-α、IL-1β浓度。DHE染色荧光检测肺组织活性氧(ROS)活性。观察肺组织病理学变化, 并进行肺损伤评分。
结果 与SEV组比较, CON组、SM组和MRS组TNF-α、IL-β浓度明显升高(P<0.05);与SM组比较, CON组与MRS组TNF-α、IL-β浓度明显升高(P<0.05)。与Sham组比较, CON组、SEV组、SM组和MRS组A3R、gp91phox蛋白含量明显升高, CON组、SM组和MRS组ROS活性明显增强, 肺损伤评分明显升高(P<0.05);与CON组比较, SEV组和SM组A3AR蛋白含量明显升高, SEV组gp91phox蛋白含量、ROS活性和肺损伤评分明显降低(P<0.05);与SEV组比较, SM组A3AR蛋白含量明显降低, gp91phox蛋白含量明显升高, SM组和MRS组ROS活性明显增强, 肺损伤评分明显升高(P<0.05)。
结论 七氟醚可以减轻机械通气诱发的肺损伤, 其作用机制是通过A3AR抑制肺脏氧化应激和炎症反应起效的。 |
| 英文摘要: |
Ojective To investigate the role and mechanism of A3 adenosine receptor (A3AR) in ventilator induced lung injury (VILI) in rats with sevoflurane inhalation.
Methods Forty male Sprague-Dawley rats weighing 200 - 250 g were randomly divided into five groups: groups Sham, CON, SEV, SM and MRS, n = 8 in each group. The VILI model was established by mechanical ventilation (VT 12 ml/kg) and continuous positive airway pressure (PEEP) for 6 h after intubation. Rats in group Sham were not ventilated. The rats in group sham were sacrificed after anesthesia with ketamine. Group CON: ketamine was used for anesthesia maintenance. Group SEV: anesthesia was maintained with 2％ sevoflurane. The A3AR inhibitor MRS1191 (1 mg/kg) administered intraperitoneally 30 min before the start of mechanical ventilation in group SM with 2％ sevoflurane was used for anesthesia maintenance. In group MRS, MRS1191 (1 mg/kg) was injected intraperitoneally 30 min before mechanical ventilation, and ketamine was used to maintain anesthesia. Rats were sacrificed at the end of the experiment. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The pathological changes of lung tissue were observed and the injury score was evaluated. The expression of A3AR and gp91phox in lung tissue was detected by Western blot. The concentration of TNF-α, IL-1β in BALF was measured. Activity of reactive oxygen species (ROS) was measured by DHE staining.
Results Compared with group SEV, the concentrations of TNF-α and IL-β in group CON, group SM and group MRS were significantly higher (P < 0.05). Compared with group SM, the concentrations of TNF-α and IL-β in group CON and group MRS increased significantly (P < 0.05). Compared with group Sham, the contents of A3AR and gp91phox protein in the other four groups increased significantly (P < 0.05). Compared with group CON and group MRS, A3AR protein content was significantly increased in group SEV and group SM, and gp91phox protein content in group SEV was significantly decreased (P < 0.05). Compared with group SEV, A3AR protein content in group SM was significantly reduced, gp91phox protein content increased significantly (P < 0.05). Compared with group Sham, ROS in group CON, group SM and group MRS was significantly increased (P < 0.05). Compared with group SEV, ROS in group SM was significantly increased (P<0.05). Compared with group CON, the lung injury score in group SEV was significantly lower. Compared with group SEV, the lung injury score in group SM and group MRS was significantly higher (P < 0.05).
Conclusion Sevoflurane can alleviate ventilator induced lung injury. The mechanism is that A3AR can inhibit oxidative stress and inflammation in lung. |
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