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| 膜联蛋白A1拟肽Ac2-26对心肺转流大鼠肺损伤的影响 |
| Effect of annexin A1 mimetic peptide Ac2-26 on pulmonary injury by cardiopulmonary bypass in rats |
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| DOI：10.12089/jca.2022.03.013 |
| 中文关键词: 膜联蛋白A1 Ac2-26 心肺转流 肺损伤 P38丝裂原活化蛋白激酶/细胞核因子-κB |
| 英文关键词: AnnexinA1 Ac2-26 Cardiopulmonary bypass Lung injury p38MAPK /NF-κB |
| 基金项目:国家自然科学基金（81760079）；贵州省卫健委科技基金（gzwjkj2020-1-136） |
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| 中文摘要: |
目的 通过观察Ac2-26对心肺转流(CPB)大鼠肺功能、肺组织结构及丝裂原活化蛋白激酶p38/细胞核因子-κB（p38MAPK/NF-κB）表达影响。
方法 选择成年健康SD雄性大鼠18只，体重350～450 g。随机分成三组：假手术组（S组）、缺血-再灌注组（IR组）和膜联蛋白A1（AnxA1）拟肽Ac2-26组（AC组），每组6只。S组做穿刺及开胸处理，不建立CPB；IR组建立CPB，10 min后开胸夹闭左肺门；AC组建立CPB，在CPB前10 min给予Ac2-26 1 mg/kg，10 min后开胸夹闭左肺门。分别在CPB前、开放左肺门时、停CPB 90 min时，记录大鼠HR、MAP，并取动脉血行血气分析，计算氧合指数（OI）、呼吸指数（RI）。停CPB 90 min时用ELISA法检测左肺组织肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）、支气管液肺泡灌洗液（BALF）中白细胞介素-6（IL-6）和总蛋白含量，采用Western-blot法检测肺组织丝裂原活化蛋白激酶p38（p38MAPK）、磷酸化丝裂原活化蛋白激酶p38（p-p38MAPK）、核因子-κBp65（NF-κBp65）、磷酸化核因子-κBp65（p-NF-κBp65）和AnxA1含量，取左肺组织行光镜检查和病理损伤评分。
结果 与S组比较，开放左肺门时、停CPB 90 min时IR组和AC组HR明显减慢，MAP、OI明显降低，RI明显升高（P<0.05），停CPB 90 min时IR组和AC组TNF-α、IL-10、IL-6、总蛋白、p-p38MAPK、p-NF-κBp65、AnxA1含量明显升高（P<0.05），病理损伤评分明显升高（P<0.05）。与IR组比较，停CPB 90 min时AC组HR明显增快，OI明显升高，RI明显降低（P<0.05），TNF-α、IL-6、总蛋白、p-p38MAPK、p-NF-κBp65、AnxA1含量明显降低（P<0.05），IL-10明显升高（P<0.05），病理损伤评分明显降低（P<0.05）。
结论 膜联蛋白A1拟肽Ac2-26可抑制大鼠CPB后肺组织丝裂原活化蛋白激酶p38的活化，抑制核因子-κB的分泌，降低TNF-α和IL-6的含量，增加IL-10含量，减轻其肺损伤程度，减少炎性渗出，改善肺功能。 |
| 英文摘要: |
Objective To investigate the effects of Ac2-26 on lung function, lung tissue structure and p38MAPK/NF-κB expression in rats undergoing cardiopulmonary bypass (CPB).
Methods Eighteen male Sprague-Dawley rats, weighing 350-450 g, were randomly divided into three groups: sham operation group (group S), ischemia-reperfusion group (group IR) and annexin A1 (AnxA1) mimetic peptide Ac2-26 group (group AC), 6 rats in each group. Group S underwent puncture and thoracotomy without CPB. In group IR, CPB was established, and the left pulmonary hilum was opened and clamped 10 minutes later. In group AC, Ac2-26 1 mg/kg was given 10 minutes before CPB, and the left pulmonary hilum was opened and clamped 10 minutes after CPB was established. HR and MAP of the rats were observed, and the arterial blood was sampled for blood gas analysis to calculate the oxygenation index (OI) and respiratory index (RI) before CPB when the left pulmonary hilum was opened and after stopping CPB for 90 minutes. After stopping CPB for 90 minutes, the contents of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in left lung tissue, interleukin-6 (IL-6) and total protein in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the contents of mitogen activated protein kinase p38 (p38MAPK), phosphorylated mitogen activated protein kinase p38 (p-p38MAPK), nuclear factor-κBp65 (NF-κBp65), phosphorylated nuclear factor-κBp65 (p-NF-κBp65)and AnxA1 in lung tissue were detected by Western blot, and the left lung tissue was taken for light microscopy and pathological injury score.
Results Compared with group S, HR, MAP and OI decreased significantly and RI increased significantly in group IR and group AC when the left pulmonary hilum was opened and after stopping CPB for 90 minutes (P < 0.05), and the contents of total protein, TNF-α, IL-6, IL-10, p-p38MAPK, p-NF-κBp65 and AnxA1 in group IR and group AC increased significantly (P < 0.05), and the pathological score increased significantly after stopping CPB for 90 minutes (P < 0.05). After stopping CPB for 90 minutes, compared with group IR, HR and OI increased significantly in group AC, RI decreased significantly (P < 0.05), and the contents of total protein, TNF-α, IL-6, p-p38MAPK, p-NF-κBp65 and AnxA1 decreased significantly (P < 0.05), IL-10 increased significantly, pathological score decreased significantly in group AC (P < 0.05) .
Conclusion AnxA1 mimetic peptide Ac2-26 can inhibit the activation of mitogen activated protein kinase p38 in ratlung tissue after CPB, inhibit the secretion of nuclear factors-κB and reduce TNF-α and IL-6, increase the content of IL-10, reduce the degree of lung injury, reduce inflammatory exudation and improve lung function. |
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