Effect of Yisui Jiedu Prescription on Apoptosis of Hippocampal Neurons Based onPI3K/Akt/Bad Signal Pathway in Rats with Vascular Dementia / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of Yisui Jiedu prescription on hippocampal neuron damage in vascular dementia (VD) rats and to regulate phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/recombinant Bcl-2 associated death promoter (Bad) mechanisms of signaling pathways of neuronal apoptosis. Method:The 40 SD rats were divided into sham operation group， model group， donepezil hydrochloride group and Yisui Jiedu prescription group， with 10 rats in each group.VD animal model was prepared by bilateral carotid artery permanent ligation (2-VO) method.The sham operation group and the model group were intragastrically administered with normal saline， the donepezil hydrochloride group was intragastrically administered with donepezil hydrochloride 0.52 mg·kg-1. The Yisui Jiedu prescription group was administered with Yisui Jiedu prescription (11.11 g·kg-1)， 1 time/d . After 30 days， Morris water maze was used to test the learning and memory ability of rats， hematoxylin-eosin (HE) staining was used to observe the histomorphological structure of hippocampal CA1 region. Ultrasound of neuron in rat hippocampal CA1 region was observed by transmission electron microscopy (TEM).Real-time fluorescent quantitative（Real-time PCR） was used to detect the Akt， Bad mRNA expression.Western blot was used to detect the Akt， p-Akt and Bad protein expression in hippocampus. Result:Compared with sham operation group， the learning and memory ability of model group decreased significantly(P<0.05). The pathological structure and neuronal ultrastructure of the hippocampus were changed obviously. Hippocampal tissue Akt mRNA and the Akt，p-Akt protein expression level decreased significantly(P<0.05)， and the levels of Bad mRNA and protein were significantly increased (P<0.05). Compared with model group， Yisui Jiedu prescription group can significantly improve the learning and memory ability of rats， improve the neuronal cells and ultrastructural changes in hippocampal CA1 area，and increase the expression of Akt mRNA and Akt，p-Akt protein in hippocampus. Decreased Bad mRNA and Bad protein expression levels (P<0.05). Conclusion:Yisui Jiedu prescription can significantly improve the learning and memory ability of VD rats， improve the ultrastructural pathological changes of hippocampus and neurons， and repair damaged neurons， which may promote Akt phosphorylation and activate PI3K/Akt/Bad. The signaling pathway plays a role in the defense of neurons against apoptosis.