呼吸机诱导肺损伤的机制探索

2020
09/23

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呼吸机诱导肺损伤的机制探索

本文由“小麻哥的日常”授权转载

分享一篇呼吸机诱导肺损伤分子机制的文章,这篇文章发表在Anesthesiology杂志上,详细内容可以下载全文获取。

死亡相关蛋白激酶1通过促进肺泡上皮细胞凋亡介导呼吸机诱导肺损伤


背景:肺泡上皮细胞凋亡与呼吸机诱导肺损伤有关。死亡相关蛋白激酶1(DAPK1)与细胞凋亡有关。假设DAPK1通过促进肺泡上皮细胞凋亡参与呼吸机诱导肺损伤。


方法:周期性牵拉诱导小鼠肺泡上皮细胞凋亡。在体外实验中分别用小干扰RNA或质粒改变DAPK1的表达。C57/BL6雄性小鼠(n=6)采用高潮气量通气建立肺损伤模型。腺相关病毒转染短发夹RNA和DAPK1抑制剂分别抑制肺中DAPK1的表达和激活。主要转归为肺泡上皮细胞凋亡和肺损伤。


结果:与对照组相比,24h周期性牵张组肺泡上皮细胞凋亡率(45±4% vs. 6±1%,P<0.0001)及DAPK1的相对表达明显增高,DAPK1基因敲除后凋亡率降低(27±5% vs. 53±8%;P<0.0001)。在没有拉伸的情况下,观察到DAPK1过度表达促进的凋亡百分比(49±6% vs. 14±3%;P<0.0001)。B细胞淋巴瘤2(BCL2)和B细胞淋巴瘤2相关X(BCL2X)的改变与DAPK1的表达有关。与低潮气量组相比,高潮气量组小鼠肺组织中DAPK1表达和肺泡上皮细胞凋亡率较高(43±6% vs. 4±2%;P<0.0001)。通过腺相关病毒转染或DAPK1抑制剂治疗抑制DAPK1似乎可以保护肺损伤,降低肺损伤评分,缓解肺部炎症,抑制肺泡上皮细胞凋亡率(47±4%和48±6%;35±5%和34±4%;P<0.0001)。


结论:DAPK1通过内源性凋亡途径诱导肺泡上皮细胞凋亡,促进呼吸机所致肺损伤的发生。

Death-associated Protein Kinase 1 Mediates Ventilator-induced Lung Injury in Mice by Promoting Alveolar Epithelial Cell Apoptosis


Background: Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis.


Methods: Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury.


Results: Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2-associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively).


Conclusions: DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice.


原文链接

Wang Y, Yang Y, Chen L, et al. Death-associated Protein Kinase 1 Mediates Ventilator-induced Lung Injury in Mice by Promoting Alveolar Epithelial Cell Apoptosis. Anesthesiology. 2020;133(4):905-918. doi:10.1097/ALN.0000000000003464

 

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本微信公众平台所刊载原创或转载内容不代表米勒之声的观点或立场。文中所涉及药物使用、疾病诊疗等内容仅供参考。

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本文由作者自行上传,并且作者对本文图文涉及知识产权负全部责任。如有侵权请及时联系(邮箱:guikequan@hmkx.cn
关键词:
呼吸机,凋亡率,机制,探索,损伤,肺泡,上皮,细胞

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