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

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 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.

Keywords:

• lung protection
• dexmedetomidine
• occludin
• ZO-1
• PI3K
• Akt
• HIF-1α

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

Data Sharing Statement

The data used to support the findings of the study are available from the corresponding author upon request.

Disclosure

The authors have no conflicts of interest to declare.