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

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 2 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 0), 40 min after OLV (T 1), and 10 min after two-lung ventilation (T 2)) 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 1 and T 2 (group D vs group N; T 1 : 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, P = 0.009; T 2 : 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.

Protective effect of Houttuynia cordata extract on propofol-induced injury of rat hippocampal neurons by regulating PI3K/Akt and Toll-like receptor 4/NF-κB signaling pathway

“…This pathway is closely related to neuronal survival because many neurotrophic factors play a protective role in the brain by activating the pathway, thus inhibiting apoptosis [ 22 ]. Similar to our findings, a previous study showed that dexmedetomidine improved propofol-induced neuronal injury in rat hippocampus through the PI3K/Akt pathway [ 23 ]. Also, this pathway had protective effects of propofol on intestinal and lung injury induced by intestinal ischemia [ 24 ].…”

Dexmedetomidine attenuates one‐lung ventilation associated lung injury by suppressing inflammatory responses: A systematic review and meta‐analysis

“…Of the 1218 potential articles in the initial search, 20 RCTs 24–43 met the inclusion criteria. The screening and selection process is demonstrated in Figure 1.…”

“…Lastly, the processes of randomization, allocation concealment and blinding were inadequate in these studies, 29–35,38–43 which indeed would cause selection bias and diagnostic bias.…”

Dexmedetomidine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting the PI3K/Akt/FoxO1 signaling pathway

“…Consistent with these findings, the present data indicated that LY294002 pretreatment markedly abolished the protective effects of DEX on LPS-induced lung inflammation, oxidative stress, and apoptosis in mice. Several studies demonstrated that pretreatment with DEX ameliorated LPS-induced acute lung injury [ 40 – 42 ], and DEX was also reported to alleviate lung ischemia–reperfusion-induced acute lung injury [ 43 ], and to alleviate lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS) lead to acute lung injury partly through activating PI3K/Akt signaling pathway [ 44 ]. However, unknown are whether DEX ameliorates LPS-induced lung inflammation, oxidative stress, and apoptosis and whether the protective effect of DEX involves the PI3K/Akt/FoxO1 signaling pathway.…”