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右美托咪定对行电视辅助胸腔镜手术患者肺保护作用及其机制的初步研究。

Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study.

机构信息

Department of Anesthesiology and Perioperative Medicine, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Nov 24;14:5155-5166. doi: 10.2147/DDDT.S276005. eCollection 2020.

Abstract

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 α 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 (T), 40 min after OLV (T), and 10 min after two-lung ventilation (T)) 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 T and T (group D vs group N; T: 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, = 0.009; T: 406.0 mmHg [392.2-423.7] vs 374.5 mmHg [340.2-378.2], = 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.

摘要

背景

电视辅助胸腔镜手术(VATS)中的肺切除术和单肺通气(OLV)可能导致急性肺损伤。右美托咪定(DEX)是一种高选择性α肾上腺素能受体激动剂,可改善成人胸外科患者的动脉氧合。本研究旨在探讨 DEX 在 VATS 患者中可能的肺保护机制。

患者和方法

本研究纳入了 74 名计划接受 VATS 的患者。在麻醉诱导前(T)、OLV 后 40 分钟(T)和双肺通气后 10 分钟(T)三个时间点采集动脉血气。同时,进行肺组织病理检查、免疫组织化学分析(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 水平以及磷酸肌醇-3-激酶(PI3K)/AKT/缺氧诱导因子(HIF)-1α信号通路的激活。还记录了术后结果,包括胸腔引流管拔除时间、住院时间、住院费用和术后肺部并发症(PPCs)。

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 和 T 时的氧合(D 组 vs N 组;T:191.8±49.8mmHg 与 159.6±48.1mmHg,=0.009;T:406.0mmHg[392.2-423.7]与 374.5mmHg[340.2-378.2],=0.001)。DEX 减轻了肺泡毛细血管上皮结构损伤,增加了 ZO-1 和 occludin 的蛋白表达,抑制了肺组织和血浆中 TNF-α和 IL-6 表达的升高,并增加了 p-PI3K、p-AKT 和 HIF-1α的蛋白表达。DEX 治疗术后肺部并发症风险较低,住院费用较低,胸腔引流管拔除时间和住院时间较短,术后结果较好。

结论

PI3K/Akt/HIF-1α信号通路的激活可能参与了 DEX 在 VATS 患者中的肺保护作用。

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