The Effect of Quercetin Activating PGC-1x/NRF-1/TFAM Signaling Pathway on Cognitive Impairment in Neonatal Rats with Hypoxic-Ischemic Brain Injury

CUI Yanyan; DONG Siqing; WANG Hui

doi:10.3639/j.issn.2095-3097.2025.06.023

Abstract：Objective To explore the impact of quercetin(Que)on cognitive impairment in neonatal rats with hy-poxic-ischemic brain damage(HIBD)by activating of PGC-1α/NRF-1/TFAM signaling pathway.Methods 144 neonatal 7-day-old SD rats were selected to establish HIBD models and randomly assigned to sham operation(Sham)group,model(HIBD)group,low and high dose Que(L-Que,H-Que)groups,positive control(Nimodipine,Nimo)group,and PGC-1α inhibitor+H-Que group,with 24 rats in each group.The Morris water maze test was used to evaluate cognitive function;the drying method was used to determine the water content of brain tissue;the infarct volume was measured using TTC staining;neuronal apoptosis was observed using TUNEL staining;Western Blot was used to detect the expression of protein related to the PGC-1α/NRF-1/TFAM signaling pathway in brain tissue.Results Compared with the Sham group,the HIBD group showed an increase in es-cape latency,mNSS score,brain tissue water content,infarct volume,and neuronal apoptosis rate to(48.67±5.14)s,(7.85±1.25)points,(89.57±3.62)%,(27.58±3.53)%,and(25.69±3.98)%,respectively,while crossings through the original platform de-creased to(1.50±0.38)times(P<0.05).Compared with the HIBD group,the escape latency of the L-Que group,H-Que group,and Nimo group decreased to(35.71±4.63)s,(26.28±4.31)s,and(24.95±4.29)s,respectively;The mNSS scores decreased to(5.80±1.02)points,(4.12±0.85)points,and(4.25±0.92)points,respectively;the brain tissue water content decreased to(82.29±3.35)%,(75.38±3.15)%,and(74.59±3.21)%,respectively;The infarct volume decreased to(16.39±3.25)%,(9.15±2.42)%,and(7.68±2.51)%,respectively;The apoptosis rates of neurons decreased to(19.06±2.69)%,(12.38±2.14)%,and(11.98±2.09)%,respectively;The number of crossings through the original platform increased to(3.00±0.35)times,(4.50±0.41)times,and(4.50±0.39)times respectively(P<0.05).Compared with the Sham group,the expression of PGC-1α,NRF-1,and TFAM pro-teins in the brain tissue of the HIBD group decreased to 0.29±0.11,0.27±0.12,and 0.25±0.09,respectively(P<0.05).Com-pared with the HIBD group,the expression of PGC-1α,NRF-1,and TFAM proteins in the brain tissue of the H-Que group increased to 0.52±0.13,0.49±0.10,and 0.41±0.09,respectively(P<0.05).Compared with the H-Que group,the addition of PGC-1α inhibitor reversed the trend of changes in the above indicators(P<0.05).Conclusion Que can improve cognitive im-pairment in neonatal rats with HIBD,and the mechanism involves the activation of PGC-1α/NRF-1/TFAM signaling pathway.