Effect of Modified Shuyu Pill on Hippocampal Neuron Apoptosis in Vascular Dementia Rats Based on ERK5 Signaling Pathway
Objective:To investigate the effect of modified Shuyu Pill on hippocampal neuron apoptosis in rats with vascular dementia(VaD).Methods:The modified bilateral common carotid artery ligation(2-VO)was used to establish the VaD rat model.One hundred and twenty rats were randomly divided into normal group,control group,model group,and treatment group,with 30 rats in each group.The treatment group was given 10 mL/(kg·d)modified Shuyu Pill by intragastric administration.The normal group,control group,and model group were given the same volume of normal saline.The intervention lasted for 8 weeks.Behavior detection were performed at the 7th day after modeling,and 4 and 8 weeks,vespectively after treatment.Histological changes of hippocampal neurons were observed by hematoxylin-eosin(HE)staining.The apoptosis of hippocampal neurons was observed by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL).The expression of mitogen-activated protein kinase K2(MEKK2),mitogen-activated protein kinase K3(MEKK3),mitogen-activated protein kinase 5(MEK5),and extracellular signal-regulated kinase 5(ERK5)were detected by immunohistochemistry.The protein expressions of MEKK2,MEKK3,MEK5,and ERK5 were detected by Western Blot.Results:Compared with the normal group and control group,the behavior of the model group was significantly different,the degeneration of neurons increased,the apoptosis rate of neurons increased(P<0.01),and the expressions of MEKK2,MEKK3,MEK5,and ERK5 decreased.Compared with the model group,the behavioral performance of the treatment group improved,the degeneration of neurons reduced,the apoptosis rate of neurons decreased(P<0.05 or P<0.01),and the expressions of MEKK2,MEKK3,MEK5,and ERK5 significantly increased.Conclusion:Modified Shuyu Pill may inhibit the apoptosis of hippocampal neurons and promote the repair of hippocampal neurons to treat VaD by up-regulating ERK5 signaling pathway.
vascular dementiamodified Shuyu Pillneuron apoptosisextracellular signal-regulated kinase 5,ERK5experimental study
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