Protective effect of NT-3 gene modified bone marrow mesenchymal stem cell transplantation on sevoflurane induced cognitive dysfunction in aged mice
Objective To explore the protective effect of NT-3 gene modified bone marrow mesenchymal stem cells(BMSCs)transplantation on sevoflurane induced cognitive dysfunction in aged mice and its mechanism.Methods Mouse BMSCs were isolated and cultured,and NT-3 gene modified BMSCs were established by lentivirus transfection.The expression of NT-3 protein was detected by Western blot.The proliferation ability of BMSCs was detected by CCK-8.The expression of neuron marker NeuN of BMSCs was detected by immunofluorescence.Forty 12-month-old C57BL/6 aged mice were randomly divided into control group,sevoflurane group,bone marrow mesenchymal stem cell group and NT-3 gene modified bone marrow mesenchymal stem cell group,with 10 mice in each group.TUNEL assay was used to detect the apoptosis of hippocampal cells of mice.The neuronal marker TH in mouse hippocampus was detected by immunofluorescence.The learning and memory ability of mice was detected by morris water maze test.The expressions of β-catenin and p-GSK-3β in the hippocampus of mice were detected by Western blot.Results BMSCs modified with NT-3 gene were successfully established.NT-3 gene modification increased the proliferation ability of BMSCs and up-regulated the NeuN expression of BMSCs.NT-3 gene modified bone marrow mesenchymal stem cell transplantation inhibited hippocampal cell apoptosis,promoted hippocampal neuron survival,increased learning and memory ability,and up-regulated β-catenin and p-GSK-3β protein expression levels in brain of sevoflurane anesthesia mice.Conclusion NT-3 gene modified bone marrow mesenchymal stem cell transplantation can improve cognitive dysfunction in sevoflurane anesthesia aged mice by activating the Wnt/β-catenin signaling pathway.
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