A Mechanism Study Underlying the Protective Effects of Cyclosporine-A on Lung Ischemia-Reperfusion Injury

Pharmacology
Jian''an LiQianjin Fang

Abstract

This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP). The apoptotic cell was detected by the TUNEL staining. Western blot was performed to analyze the protein expression levels. CsA not only attenuated the histopathologic alterations in lung and mitochondria after I/R injury, but also attenuated I/R injury through increasing MPP and inhibiting MPTP opening. Besides, CsA attenuated I/R injury through suppressing the release of cytochrome-c (CytC), inhibiting cell apoptosis and decreasing the expression levels of cyclophilin-D (Cyp-D), adenine nucleotide translocase 1 (ANT1) and voltage-dependent anion channel 1 (VDAC1). Finally, we found that Cyp-D knockdown inhibits I/R injury-induced MPTP opening and cell apoptosis. Our study found that the protective role of CsA on lung I/R injury depends on the inhibition of MPT...Continue Reading

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Citations

Mar 5, 2020·Proteomics·Venkateswaran NatarajanKarthik Mallilankaraman
Dec 19, 2018·Biomolecules·George A Porter, Gisela Beutner
Jun 4, 2020·Critical Care : the Official Journal of the Critical Care Forum·Martin CourLaurent Argaud
May 23, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Hailey M ShepherdDaniel Kreisel
Jul 8, 2021·Translational Vision Science & Technology·Marco H JiEdward H Wood

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis