Ghrelin-mediated HO-1/PGC-1α signaling pathway regulates mitochondrial oxidative stress to improve traumatic brain injury in rats
10.12007/j.issn.0258-4646.2025.04.012
- VernacularTitle:Ghrelin介导HO-1/PGC-1α信号通路调节线粒体氧化应激改善大鼠创伤性脑损伤
- Author:
Zhihui ZHAO
1
;
Xiuli ZHAI
1
;
Jing WANG
1
;
Min MA
1
;
Xianghua BAI
1
;
Nan SU
1
Author Information
1. 内蒙古自治区人民医院麻醉科,呼和浩特 010017
- Publication Type:Journal Article
- Keywords:
Chrelin;
traumatic brain injury;
rat;
HO-1/PGC-1α signaling pathway;
oxidative stress
- From:
Journal of China Medical University
2025;54(4):351-358
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of Ghrelin on traumatic brain injury(TBI)in rats based on the HO-1/PGC-1αsignaling pathway.Methods Thirty SPF male rats were randomly divided into sham,TBI,and Ghrelin groups,with 10 rats in each group.A TBI rat model was established using the Feeney free-fall impingement method.The Ghrelin group was injected by caudal vein at a dose of 20 μg/kg 30 min after modeling,while the sham group was not impinged.After 72 h of modeling,the brain tissues of the rats were col-lected,and the brain water content was measured in order to analyze the severity of brain edema.HE staining was used to observe patho-logical changes in brain tissue.The levels of the oxidative stress factors MDA,SOD,and GSH-Px were determined using ELISA.TUNEL staining was used to detect the apoptosis of the brain cells,and the expression levels of Bcl-2,Bax,caspase-3 and caspase-9 in the brain tissues were detected by Western blotting.Mitochondrial reactive oxygen species(mtROS)in the brain tissues were detected by immuno-fluorescence.Mitochondrial function indicators,including mitochondrial mitogen Mfn 1/2,nuclear respiration factor 1(NRF1),and mito-chondrial transcription factor A(TFAM)were detected by Western blotting.The expression levels of HO-1 and PGC-1α in the brain tis-sues of rats in each group were detected by Western blotting.Twenty TBI model rats treated with Ghrelin were divided into Ghrelin+sh-NC and Ghrelin+sh-HMOX1 group with 10 rats in each group.Rats were treated with Ghrelin and injected with knock-down control(adenovirus 2.5 × 109 pfu)or knock-down HMOX1 adenovirus(2.5 × 109 pfu)via tail vein.Western blotting was used to detect the expressions of HO-1,PGC-1 α,Bcl-2,Bax,caspase-3 and caspase-9 in the brain tissues of the two groups.The levels of MDA,SOD and GSH-Px in brain tissue of two groups were detected by ELISA.Results Compared with the sham group,the pathological injury and brain edema in TBI group were aggravated,the number of brain cell apoptosis increased,the levels of oxidative stress factors SOD and GSH-Px decreased,the level of MDA increased,the level of mtROS in brain tissue decreased,the expressions of Bax,caspase-3 and caspase-9 increased,and the expressions of Mfn1/2,NRF1,TFAM,HO-1 and PGC-1α decreased(P＜0.05).Compared with TBI group,the pathological damage of brain tissue in Ghrelin group was improved,the brain edema was alleviated,the number of brain cell apoptosis was reduced,the levels of oxidative stress factors SOD and GSH-Px were increased,the level of MDA was decreased,the mtROS in brain tissue was decreased,the expression of Bcl-2 protein was increased,the expressions of Bax,caspase-3 and caspase-9 protein were decreased,and the expressions of Mfn1/2,NRF1,TFAM,HO-1 and PGC-1α were decreased(P＜0.05).Compared with Ghrelin+sh-NC group,the expressions of Bax,caspase-3 and caspase-9,MDA in brain tissue of Ghrelin+sh-HMOX1 group increased,while the levels of SOD and GSH-Px decreased(P＜0.05).Conclusion Chrelin has protective effect on TBI in rats,and can inhibit brain tissue injury and apoptosis in rats.Its mechanism may be achieved by regulating mitochondrial oxidative stress through HO-1/PGC-1α signaling pathway.
