A Study Of Effects On Genes In Notch Signaling Pathway And Astrocyte From Vascular Congnitive Impairment Rats By Shouwuyizhi Capsule

Objective: The morbidity and mortality of Vascular cognitive impairment (VCI) has been higher and higher in recent years. It has become an important common sanitation problem.The interaction between Neurons and Astrocytes is the key factor of the neuron survival during cerebral ischemic injury. In this study, we explored the effects of ShouWuYiZhi capsule on astrocytes and investigated the mechanism of genes expression in Notch signaling pathway,and therefore provides the experimental data and theoretical base for the treatment from the cellular level and gene regulation of ShouWuYiZhi Capsule for vascular cognitive impairment.Methods: Sprague-Dawley rats were used for VCI model establishment. 80 rats were screened after Morris water maze test and randomly divided into 4 groups: sham operation group, model group, piracetam group and Shouwuyizhi Capsule group, and each group has 20 rats. After 4-week administration, behavioral change of rat was recorded by Morris water maze. Histomorphological changes of neuron in hippocampal CA1 region were analysed after Nissl staining and ultrastructure alternation was observed via transmission electric microscope. GFAP and NGF expression were measured by immunohistochemistry and the expression of the genes of Notch1, PS1, Hes3, Stat3, GFAP,?-APP were measured using real time PCR.Results: The results of Morris water maze showed that assessment of orientation test and spatial probe test from ShouWuYiZhi Capsule group were significantly higher than model group and Piracetam group (P <0.01).Compared with model group and Piracetam group, Neuron in the hippocampus cone of Shouwuyizhi Capsule group was more orderliness and confertim, and Nissl bodies were richer in cytoplasm. No obvious ultrastructure change of organelles was observed in ShouWuYiZhi Capsule group compared with sham operation group.Expression of GFAP and NGF was higher in ShouWuYiZhi Capsule group than in model group or Piracetam group (P<0.01).Expression of Notch1?Hes3?Stat3 and PS1 in ShouWuYiZhi Capsule group were increased significantly(V.S. model group P<0.01, V.S. Piracetam group P<0.05, respectively). Compared with model group and Piracetam group, the expression of GFAP gene was enhanced significantly(P<0.01). Compared with model group, the expression of?-APP gene of Shouwuyizhi Capsule group was decreased significantly(P<0.05), while no difference was showed compared with Piracetam group.Conclusion: 1) ShouWuYiZhi capsule could Protect neurons against cerebral ischemic injury, and maintain the integrity of neurons'structure and function. 2) Mechanism of neuroprotection of ShouWuYiZhi capsule might be involved in the promotion of Notch1, Hes3, Stat3, and GFAP expression and the induction of differentiation neural stem cells to astrocytes and the production of NGF as well as the reduction of apoptotic neurons in VCI model, which might be the main factor contribute to neuron protection, neurotrophy, renovation and regeneration. 3)ShouWuYiZhi capsule could reduce the impairment of A?against nerve cell and ameliorate the learning and memory capability due to decreasing the expression of PS1 and?-APP. 4) ShouWuYiZhi capsule could improve the learning and memory ability of VCI model rats, and ShouWuYiZhi capsule is a valid therapy to VCI,which might be more effective than piracetam.