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Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-11-24 , DOI: 10.2147/dddt.s276005
Linjia Zhu 1 , Yang Zhang 1 , Zhenfeng Zhang 1 , Xiahao Ding 1 , Chanjuan Gong 1 , Yanning Qian 1
Affiliation  

Background: Lung resection and one lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS) may lead to acute lung injury. Dexmedetomidine (DEX), a highly selective α2 adrenergic receptor agonist, improves arterial oxygenation in adult patients undergoing thoracic surgery. The aim of this pilot study was to explore possible mechanism related to lung protection of DEX in patients undergoing VATS.
Patients and Methods: Seventy-four patients scheduled for VATS were enrolled in this study. Three timepoints (before anesthesia induction (T0), 40 min after OLV (T1), and 10 min after two-lung ventilation (T2)) of arterial blood gas were obtained. Meanwhile, lung histopathologic examination, immunohistochemistry analysis (occludin and ZO-1), levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lung tissue and plasma, and activation of phosphoinositide-3-kinase (PI3K)/AKT/hypoxia-inducible factor (HIF)-1α signaling were detected. Postoperative outcomes including duration of withdrawing the pleural drainage tube, length of hospital stay, hospitalization expenses, and postoperative pulmonary complications (PPCs) were also recorded.
Results: Sixty-seven patients were randomly divided into DEX group (group D, n=33) and control group (group N, n=34). DEX improved oxygenation at T1 and T2 (group D vs group N; T1: 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, P = 0.009; T2: 406.0 mmHg [392.2– 423.7] vs 374.5 mmHg [340.2– 378.2], P = 0.001). DEX alleviated the alveolar capillary epithelial structure damage, increased protein expression of ZO-1 and occludin, inhibited elevation of the expression of TNF-α and IL-6 in lung tissue and plasma, and increased protein expression of p-PI3K, p-AKT and HIF-1α. Dex administered had better postoperative outcomes with less risk of PPCs and hospitalization expenses as well as shorter duration of withdrawing the pleural drainage tube and length of hospital stay.
Conclusion: Activation of PI3K/Akt/HIF-1α signaling might be involved in lung protection of DEX in patients undergoing VATS.



中文翻译:

PI3K/Akt/HIF-1α 信号通路的激活与接受视频辅助胸腔镜手术的患者右美托咪定的肺保护有关:一项初步研究

背景:电视胸腔镜手术 (VATS) 期间的肺切除和单肺通气 (OLV) 可能导致急性肺损伤。右美托咪定 (DEX) 是一种高选择性 α 2肾上腺素能受体激动剂,可改善接受胸外科手术的成年患者的动脉氧合。这项初步研究的目的是探索与 DEX 对接受 VATS 患者的肺保护相关的可能机制。
患者和方法:本研究招募了 74 名计划进行 VATS 的患者。三个时间点(麻醉诱导前(T 0)、OLV 后 40 分钟(T 1)和双肺通气后 10 分钟(T 2)) 获得动脉血气。同时,肺组织病理学检查、免疫组化分析(occludin和ZO-1)、肺组织和血浆中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的水平,以及磷酸肌醇3-激酶(PI3K)的激活情况。检测到 /AKT/缺氧诱导因子 (HIF)-1α 信号传导。还记录了术后结果,包括拔出胸膜引流管的时间、住院时间、住院费用和术后肺部并发症(PPC)。
结果: 67例患者随机分为DEX组(D组,n=33)和对照组(N组,n=34)。DEX 改善了 T 1和 T 2的氧合(D 组与 N 组;T 1:191.8 ± 49.8 mmHg 与 159.6 ± 48.1 mmHg,P = 0.009;T 2 : 406.0 mmHg [392.2–423.7] 与 374.5 mmHg [340.2– 378.2],P = 0.001)。DEX减轻肺泡毛细血管上皮结构损伤,增加ZO-1和occludin蛋白表达,抑制肺组织和血浆中TNF-α和IL-6表达升高,增加p-PI3K、p-AKT蛋白表达和 HIF-1α。Dex 的术后结果更好,PPC 风险和住院费用更低,胸膜引流管拔出时间和住院时间更短。
结论: PI3K/Akt/HIF-1α信号通路的激活可能参与了VATS患者DEX的肺保护作用。

更新日期:2020-11-25
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