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Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NFκB signaling pathway

 Dong Woo Han  ;  Ju Eun Oh  ;  Beom Jin Lim  ;  Yeonseung Han  ;  Young Song 
 KOREAN JOURNAL OF ANESTHESIOLOGY, Vol.75(6) : 518-529, 2022-12 
Journal Title
Issue Date
Acute Lung Injury* / complications ; Acute Lung Injury* / prevention & control ; Animals ; Autophagy ; Dexmedetomidine* / pharmacology ; Interleukin-6 / therapeutic use ; Male ; NF-kappa B / metabolism ; Pulmonary Edema* / complications ; Pulmonary Edema* / prevention & control ; Rats ; Rats, Wistar ; Signal Transduction ; Subarachnoid Hemorrhage* / complications ; Subarachnoid Hemorrhage* / drug therapy ; Toll-Like Receptor 4 / metabolism ; Toll-Like Receptor 9 / metabolism
Acute lung injury ; Autophagy ; Dexmedetomidine ; Inflammation ; Subarachnoid hemorrhage ; Toll-like receptors
Background: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX).

Methods: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of DEX, respectively. Histological ALI score and pulmonary edema were assessed after 48 h. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1β, IFN-γ, and TNFα were also assessed.

Results: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P < 0.001 for both) and SAH+DEX25 groups (P = 0.001 and P < 0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group.

Conclusions: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Song, Young(송영) ORCID logo https://orcid.org/0000-0003-4597-387X
Oh, Ju Eun(오주은)
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
Han, Dong Woo(한동우) ORCID logo https://orcid.org/0000-0002-8757-663X
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