Effects of mesenchymal stem cells on ferroptosis in experimental autoimmune encephalomyelitis mice
Objective To investigate the effects of mesenchymal stem cells(MSCs)treatment on ferroptosis and ex-pressions of key regulatory proteins in experimental autoimmune encephalomyelitis(EAE)mice.Methods The body weights and symptom scores of mice were evaluated daily.To assess conditions of inflammation and myelination in spi-nal cord,the sections were respectively stained.The contents of reduced glutathione(GSH),malondialdehyde(MDA)and total superoxide dismutase(T-SOD)were tested to detect ferroptosis.The protein expressions of transferrin receptor 1(TFR1),acyl-CoA synthetase long-chain family 4(ACSL4),glutathione peroxidase 4(GPX4)and ferroptosis sup-pressor protein 1(FSP1)were detected with Western blotting.Results MSCs treatment alleviated weight loss and symptoms of EAE mice.Pathologically,MSCs improved infiltration of inflammatory cells and remyelination of mice.MSCs upregulated the contents of GSH in spinal cord and brain(P<0.01,P<0.05),as well as T-SOD in spinal cord(P<0.01),and downregulated MDA concentration in brain(P<0.05).Besides,MSCs reduced the protein expressions of TFR1(P<0.05,P<0.01)and ACSL4(P<0.05,P<0.001),increased the protein expressions of FSP1(both P<0.05)in spinal cord and brain.Also,the protein expression of GPX4 in brain was promoted after MSCs treatment(P<0.05).Conclusion MSCs play a therapeutic role in inhibiting ferroptosis in EAE mice by regulating iron metabolism,lipid metabolism and promoting reactive oxygen species clearance.
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