Protein profiling indentified neuroprotection effect after corticosterone intervention in rats with traumatic brain injury

doi:10.3877/cma.j.issn.2095-9141.2025.01.003

Abstract

Abstract:

Objective

To explore the neuroprotective effect of corticosterone （CORT） on acute traumatic brain injury （TBI） through quantitative proteomics.

Methods

Fifteen male Sprague-Dawley（SD） rats were selected and randomly divided into a sham operation group，a TBI model group，and a CORT treatment group，with 5 rats in each group. A rat TBI model was established using controlled cortical impact （CCI）. The operation steps of the sham operation group were the same as those of the TBI model group，except that the cortex was not impacted. The CORT treatment group was intraperitoneally injected with CORT （0.3 mg/kg） within 1 h after impact，once a day for 2 consecutive days. At 48 h after TBI，ultra-high performance liquid chromatography and isobaric tags for relative and absolute quantitation（iTRAQ） protein mass spectrometry were used to analyze the differential proteins in the hippocampal tissues between the TBI model group and the CORT treatment group. OmicStudio tools，the Gene Ontology （GO） database，Ingenuity Pathway Analysis （IPA） software，and Cytoscape software were used to plot and analyze the volcano plot of differential protein expression，cellular components，biological processes and molecular functions，canonical enrichment pathways，and the interactions between proteins，respectively.

Results

The results of protein mass spectrometry data showed that a total of 3134 proteins were identified，and there were 71 differentially expressed proteins between the CORT treatment group and the TBI model group. The results of the volcano plot showed that，compared with the TBI model group，there were 28 up-regulated differential proteins ［fold change （FC）≥1.5） and 32 down-regulated differential proteins （FC≤0.65） in the CORT treatment group. The results of bioinformatics analysis （GO and IPA enrichment of canonical pathways） showed that the enriched canonical pathways included liver X receptor/retinoid X receptor （RXR） activation ［-log₁₀（P）=6.96］，farnesoid X receptor/RXR activation ［-log₁₀（P）=6.84］，acute phase response signaling pathway ［-log₁₀（P）=5.81］，etc.. The top 5 proteins in the interaction nodes among the differential proteins included α-1-antichymotrypsin，serum transferrin，plasminogen，complement C3，cytochrome C，etc..

Conclusion

The mechanism of the neuroprotective effect of CORT on TBI may involve regulating coagulation disorders，promoting iron homeostasis，reducing lipid peroxidation，the response to the acute phase，and anti-apoptosis.

Key words: Traumatic brain injury, Biomarkers, Proteomics, Corticosterone, iTRAQ, Neuroprotection

Yifan Lyu, Bin Zhang, Xiang Mao, Baiyun Liu, Guoyi Gao, Fei Niu. Protein profiling indentified neuroprotection effect after corticosterone intervention in rats with traumatic brain injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2025, 11(01): 17-25.

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Figures/Tables 6

References 19

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编号	蛋白名称	基因名	CORT/TBI（差异倍数≤0.65与≥1.5）	P值
P54311	Guanine nucleotide-binding protein G（I）/G（S）/G（T） subunit beta-1	Gnb1	0.046	0.007
P24090	Alpha-2-HS-glycoprotein	Ahsg	0.063	0.042
P68255	14-3-3 protein theta	Ywhaq	0.104	0.003
P62747	Rho-related GTP-binding protein RhoB	Rhob	0.119	0.009
P00787	Cathepsin B	Ctsb	0.134	0.014
P09606	Glutamine synthetase	Glul	0.143	0.022
Q01177	Plasminogen	Plg	0.167	0.001
Q05962	ADP/ATP translocase 1	Slc25a4	0.167	0.034
P12346	Serotransferrin	Tf	0.185	＜0.001
P62898	Cytochrome c， somatic	Cycs	0.192	0.007
P29117	Peptidyl-prolyl cis-trans isomerase F， mitochondrial	Ppif	0.207	0.022
P46101	Dipeptidyl aminopeptidase-like protein 6	Dpp6	0.286	＜0.001
B0BNE5	S-formylglutathione hydrolase	Esd	0.288	0.019
P20059	Hemopexin	Hpx	0.302	0.016
Q8CFN2	Cell division control protein 42 homolog	Cdc42	0.331	0.040
P04276	Vitamin D-binding protein	Gc	0.350	＜0.001
P01946	Hemoglobin subunit alpha-1/2	Hba1	0.363	＜0.001
Q6P6R2	Dihydrolipoyl dehydrogenase， mitochondrial	Dld	0.373	0.005
P18266	Glycogen synthase kinase-3 beta	Gsk3b	0.413	0.012
P07150	Annexin A1	Anxa1	0.425	0.001
P01026	Complement C3	C3	0.440	＜0.001
Q9QYF3	Unconventional myin-Va	Myo5a	0.466	0.003
Q8CHM7	2-hydroxyacyl-CoA lyase 1	Hacl1	0.492	0.026
P63102	14-3-3 protein zeta/delta	Ywhaz	0.496	0.037
Q6UPE1	Electron transfer flavoprotein-ubiquinone oxidoreductase， mitochondrial	Etfdh	0.515	0.001
P06687	Sodium/potassium-transporting ATPase subunit alpha-3	Atp1a3	0.540	0.019
P04636	Malate dehydrogenase， mitochondrial	Mdh2	0.550	0.013
Q08602	Geranylgeranyl transferase type-2 subunit alpha	Rabggta	0.570	0.012
P17475	Alpha-1-antiproteinase	Serpina1	0.586	0.010
Q62915	REVERSED Peripheral plasma membrane protein CASK	Cask	0.586	0.042
Q63041	Alpha-1-macroglobulin	A1m	0.614	0.020
O35180	Endophilin-A3	Sh3gl3	0.631	0.032
P34926	Microtubule-associated protein 1A	Map1a	1.514	0.033
Q62824	Exocyst complex component 4	Exoc4	1.514	0.036
P61265	Syntaxin-1B	Stx1b	1.514	0.037
O55166	Vacuolar protein sorting-associated protein 52 homolog	Vps52	1.556	0.028
P09527	Ras-related protein Rab-7a	Rab7a	1.629	0.032
P07335	Creatine kinase B-type	Ckb	1.675	0.043
A1L1I3	Numb-like protein	Numbl	1.706	0.016
O35550	Rab GTPase-binding effector protein 1	Rabep1	1.706	0.044
P29457	Serpin H1	Serpinh1	1.738	0.028
P35281	Ras-related protein Rab-10	Rab10	1.754	0.045
Q63560	Microtubule-associated protein 6	Map6	1.770	0.004
Q5U300	Ubiquitin-like modifier-activating enzyme 1	Uba1	1.770	0.020
P10888	Cytochrome c oxidase subunit 4 isoform 1， mitochondrial	Cox4i1	1.836	0.034
Q924S5	Lon protease homolog， mitochondrial	Lonp1	1.888	0.047
P11915	Non-specific lipid-transfer protein	Scp2	1.959	0.016
Q9ERH3	WD repeat-containing protein 7	Wdr7	1.995	0.009
P16086	Spectrin alpha chain， non-erythrocytic 1	Sptan1	2.032	＜0.001
Q62936	Disks large homolog 3	Dlg3	2.051	0.005
Q9QWN8	Spectrin beta chain， non-erythrocytic 2	Sptbn2	2.089	0.003
P11507	Sarcoplasmic/endoplasmic reticulum calcium ATPase 2	Atp2a2	2.228	0.035
Q60587	Trifunctional enzyme subunit beta， mitochondrial	Hadhb	2.333	0.009
P60881	Synaptomal-associated protein 25	Snap25	2.399	0.045
P18886	Carnitine O-palmitoyltransferase 2， mitochondrial	Cpt2	2.443	0.007
Q04400	Adenylate cyclase type 5	Adcy5	2.729	0.009
Q80WF4	Transmembrane protein 132A	Tmem132a	2.780	0.007
Q6IFW6	Keratin， type I cytkeletal 10	Krt10	2.884	0.015
O08719	Ena/VASP-like protein	Evl	2.992	0.040
Q5EGZ1	Angiotensin-converting enzyme 2	Ace2	6.138	0.037

编号	蛋白名称	基因名	CORT/TBI（差异倍数≤0.65与≥1.5）	P值
P54311	Guanine nucleotide-binding protein G（I）/G（S）/G（T） subunit beta-1	Gnb1	0.046	0.007
P24090	Alpha-2-HS-glycoprotein	Ahsg	0.063	0.042
P68255	14-3-3 protein theta	Ywhaq	0.104	0.003
P62747	Rho-related GTP-binding protein RhoB	Rhob	0.119	0.009
P00787	Cathepsin B	Ctsb	0.134	0.014
P09606	Glutamine synthetase	Glul	0.143	0.022
Q01177	Plasminogen	Plg	0.167	0.001
Q05962	ADP/ATP translocase 1	Slc25a4	0.167	0.034
P12346	Serotransferrin	Tf	0.185	＜0.001
P62898	Cytochrome c， somatic	Cycs	0.192	0.007
P29117	Peptidyl-prolyl cis-trans isomerase F， mitochondrial	Ppif	0.207	0.022
P46101	Dipeptidyl aminopeptidase-like protein 6	Dpp6	0.286	＜0.001
B0BNE5	S-formylglutathione hydrolase	Esd	0.288	0.019
P20059	Hemopexin	Hpx	0.302	0.016
Q8CFN2	Cell division control protein 42 homolog	Cdc42	0.331	0.040
P04276	Vitamin D-binding protein	Gc	0.350	＜0.001
P01946	Hemoglobin subunit alpha-1/2	Hba1	0.363	＜0.001
Q6P6R2	Dihydrolipoyl dehydrogenase， mitochondrial	Dld	0.373	0.005
P18266	Glycogen synthase kinase-3 beta	Gsk3b	0.413	0.012
P07150	Annexin A1	Anxa1	0.425	0.001
P01026	Complement C3	C3	0.440	＜0.001
Q9QYF3	Unconventional myin-Va	Myo5a	0.466	0.003
Q8CHM7	2-hydroxyacyl-CoA lyase 1	Hacl1	0.492	0.026
P63102	14-3-3 protein zeta/delta	Ywhaz	0.496	0.037
Q6UPE1	Electron transfer flavoprotein-ubiquinone oxidoreductase， mitochondrial	Etfdh	0.515	0.001
P06687	Sodium/potassium-transporting ATPase subunit alpha-3	Atp1a3	0.540	0.019
P04636	Malate dehydrogenase， mitochondrial	Mdh2	0.550	0.013
Q08602	Geranylgeranyl transferase type-2 subunit alpha	Rabggta	0.570	0.012
P17475	Alpha-1-antiproteinase	Serpina1	0.586	0.010
Q62915	REVERSED Peripheral plasma membrane protein CASK	Cask	0.586	0.042
Q63041	Alpha-1-macroglobulin	A1m	0.614	0.020
O35180	Endophilin-A3	Sh3gl3	0.631	0.032
P34926	Microtubule-associated protein 1A	Map1a	1.514	0.033
Q62824	Exocyst complex component 4	Exoc4	1.514	0.036
P61265	Syntaxin-1B	Stx1b	1.514	0.037
O55166	Vacuolar protein sorting-associated protein 52 homolog	Vps52	1.556	0.028
P09527	Ras-related protein Rab-7a	Rab7a	1.629	0.032
P07335	Creatine kinase B-type	Ckb	1.675	0.043
A1L1I3	Numb-like protein	Numbl	1.706	0.016
O35550	Rab GTPase-binding effector protein 1	Rabep1	1.706	0.044
P29457	Serpin H1	Serpinh1	1.738	0.028
P35281	Ras-related protein Rab-10	Rab10	1.754	0.045
Q63560	Microtubule-associated protein 6	Map6	1.770	0.004
Q5U300	Ubiquitin-like modifier-activating enzyme 1	Uba1	1.770	0.020
P10888	Cytochrome c oxidase subunit 4 isoform 1， mitochondrial	Cox4i1	1.836	0.034
Q924S5	Lon protease homolog， mitochondrial	Lonp1	1.888	0.047
P11915	Non-specific lipid-transfer protein	Scp2	1.959	0.016
Q9ERH3	WD repeat-containing protein 7	Wdr7	1.995	0.009
P16086	Spectrin alpha chain， non-erythrocytic 1	Sptan1	2.032	＜0.001
Q62936	Disks large homolog 3	Dlg3	2.051	0.005
Q9QWN8	Spectrin beta chain， non-erythrocytic 2	Sptbn2	2.089	0.003
P11507	Sarcoplasmic/endoplasmic reticulum calcium ATPase 2	Atp2a2	2.228	0.035
Q60587	Trifunctional enzyme subunit beta， mitochondrial	Hadhb	2.333	0.009
P60881	Synaptomal-associated protein 25	Snap25	2.399	0.045
P18886	Carnitine O-palmitoyltransferase 2， mitochondrial	Cpt2	2.443	0.007
Q04400	Adenylate cyclase type 5	Adcy5	2.729	0.009
Q80WF4	Transmembrane protein 132A	Tmem132a	2.780	0.007
Q6IFW6	Keratin， type I cytkeletal 10	Krt10	2.884	0.015
O08719	Ena/VASP-like protein	Evl	2.992	0.040
Q5EGZ1	Angiotensin-converting enzyme 2	Ace2	6.138	0.037

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