Protective Effect of Calpain Inhibition During Cold Ischemia on Ischemia-reperfusion Injury After Lung Transplantation.

Autor:	Matsui Y; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Kanou T; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Matsui T; Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan., Fukui E; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Kimura T; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Ose N; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Funaki S; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan., Shintani Y; Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2023 Sep 01; Vol. 107 (9), pp. 1945-1954. Date of Electronic Publication: 2023 Aug 21.
DOI:	10.1097/TP.0000000000004515
Abstrakt:	Background: Necroptosis, one of the types of regulated necrosis, causes ischemia-reperfusion (IR) lung injury. N-acetyl-leucyl-leucyl-norleucinal (ALLN), a calpain inhibitor, is known to attenuate necroptosis and apoptosis, and the purpose of this study was to evaluate the protective effect of ALLN during cold ischemia against IR injury in a rat lung transplant model. Methods: Male Lewis rats (250-350 g) were divided into 3 groups: sham group (n = 4), nontransplantation; control group (n = 8), transplantation with IR lung injury; and ALLN group (n = 8), transplantation with IR lung injury/ALLN. Rats in the sham group underwent a simple thoracotomy, and the remaining 2 groups of rats underwent an orthotopic left lung transplant. Cold ischemic time was 15 h. After 2 h of reperfusion, physiological function, inflammatory cytokine expression, pathway activation, and the degrees of necroptosis and apoptosis were evaluated. Results: Lung gas exchange (PaO 2 /FiO 2 ) was significantly better, and pulmonary edema was significantly improved in the ALLN group compared with the control group ( P = 0.0009, P = 0.0014). Plasma expression of interleukin-1β was significantly lower in the ALLN group than in the control group ( P = 0.0313). The proportion of necroptotic and apoptotic cells was significantly lower in the ALLN group than in the control group ( P = 0.0009), whereas the proportion of apoptotic cells remained unchanged ( P = 0.372); therefore, the calpain inhibitor was thought to suppress necroptosis. Conclusions: The administration of ALLN during cold ischemia appears to improve IR lung injury in a lung transplant animal model via the inhibition of necroptosis. Competing Interests: The authors declare no conflicts of interest. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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