Mechanism of tetramethylpyrazine combined with neural stem cells transplantation on cerebral ischemia-reperfusion rats
This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP)combined with transplantation of neural stem cells(NSCs)on middle cerebral artery occlusion(MCAO)rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior.MCAO rats were randomly divided into a model group,a TMP group,an NSCs transplantation group,and a TMP combined with NSCs transplantation group according to neu-rological function scores.A sham group was set up at the same time.The neurological function score was used to evaluate the improve-ment of neurological function in MCAO rats after TMP combined with NSCs transplantation.The proliferation,migration,and differen-tiation of NSCs were evaluated by BrdU,BrdU/DCX,BrdU/NeuN,and BrdU/GFAP immunofluorescence labeling.The protein ex-pression of stromal cell-derived factor 1(SDF-1),C-X-C motif chemokine receptor 4(CXCR4),as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2),Kelch-like ECH-associated protein 1(KEAP1),heme oxygenase 1(HO-1),NAD(P)H quinone oxidoreductase 1(NQO1)was detected by Western blot to study the migration mechanism of TMP combined with NSCs.The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats.Immunofluorescence staining showed a significant increase in the number of BrdU+,BrdU+/DCX+,BrdU+/NeuN+,and BrdU+/GFAP+cells in the TMP,NSCs transplantation,and combined treatment groups,with the combined treatment group showing the most significant increase.Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP,NSCs transplantation,and combined treatment groups,along with up-regulated protein expression of Nrf2,HO-1,and NQO1,and de-creased KEAP1 protein expression.This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation,migration,and differentiation of NSCs,and the effect of TMP combined with NSCs transplanta-tion is superior.The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.
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