Effect of PGC-1α on cerebral ischemia-reperfusion injury after cardiac arrest and resuscitation

WANG Chao; WANG Li-fen; HU Hai-yan

doi:10.13820/j.cnki.gdyx.20243370

Abstract：Objective To investigate the effects and mechanisms of peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)on cerebral ischemia-reperfusion injury after resuscitation of cardiac arrest.Methods Eighteen Sprague-Dawley rats with stable vital signs were acclimated for one week and randomly divided into two groups by envelope method:a resuscitation group and a PGC-1α group.A cardiac arrest model was established in all rats,and after successful cardiopulmonary resuscitation(CPR),rats in the PGC-1α group received intravenous injection of a PGC-1α activator via the femoral vein,while the resuscitation group received saline.Time of death was recorded.After 24 hours of survival,rats were euthanized under anesthesia and brain tissue samples were collected.Hematoxylin-eosin(HE)staining was used to observe brain pathology;ATP levels in brain tissue were measured using an ATP assay kit;RT-PCR was used to detect mRNA expression of IL-6 and TNF-α;and Western blot(WB)was performed to assess the protein levels of IL-6 and TNF-α in brain tissue.Results In the resuscitation group,brain tissue showed disor-ganized structure,extensive vacuole formation,cytoplasmic shrinkage,nuclear pyknosis,and significant inflammatory cell infiltration.In contrast,the PGC-1α group exhibited relatively intact brain structure,fewer vacuoles,and reduced in-flammation.The ATP content in brain tissue was significantly higher in the PGC-1α group than in the resuscitation group(F=2.80,P＜0.001).Expression of inflammatory cytokines IL-6 and TNF-α,both at the mRNA and protein levels,was significantly lower in the PGC-1α group(F=3.95,P=0.001 9;F=1.67,P＜0.001;t=23.78,P＜0.000 1;t=146.8,P＜0.000 1).Conclusion PGC-1α plays a protective role in cerebral ischemia-reperfusion injury following cardiac arrest and resuscitation,possibly by enhancing mitochondrial energy metabolism and reducing inflammatory responses.