The protective mechanisms of hippocampal neurons on RhoA/ROCK2 pathway mediated by Rho kinase inhibitors in vascular dementia rats / 中风与神经疾病杂志

ABSTRACT

@#Objective　To investigate the protective mechanism of Rho protein kinase 2 (ROCK2) inhibitor constructed based on adeno-associated virus vector on vascular dementia (VaD) rat hippocampal neurons.Methods　Forty SD rats were randomly divided into sham operation group,model group,ROCK2 interference group (shROCK2),negative control group.The VaD model was prepared by permanent ligation of bilateral common carotid arteries.AAV9-ROCK2-shRNA was injected into the hippocampus of the rat by stereotaxic technique,the negative control group was injected with the same amount of empty vector adeno-associated virus.After 4 weeks,morris water maze was used to test the learning and memory abilities of rats.RT-PCR and Western blot were used to detect the mRNA and protein expression levels of RhoA,ROCK2,MLC,MLCP.Results　Four weeks after operation.The mRNA and protein expressions of the above 4 indicators in hippocampus increased (P<0.01),the synaptic vesicles disappeared,and the structure of hippocampus was chaotic in the model group.Compared with the model and control group,the learning and memory ability of rats in ROCK2 interference group was significantly improved,the mRNA and protein of the above 4 indicators were significantly decreased (P<0.05),and the pre-synaptic vesicles were normal and the organelles were more complete.Conclusion　Rho protein kinase 2 inhibitors can reduce the expression of downstream related proteins by inhibiting RhoA/ROCK2 signaling pathway,then promote neuronal axon regeneration and alleviate cognitive dysfunction of VaD rats.