| Objective:The current study aims to observe the effect of Tongluoxingnao effervescent tablet on cognitive function, cerebral blood flow support and expression of energy metabolism-related proteins in multi-infarct dementia rats;to explore the relationship of between improving memory effect and brain energy metabolism;to reveal the mechanism of Tongluoxingnao effervescent tablet on curing dementia.Method:1.Model Establishment We establish multi-infarct dementia rat model induced by thrombus. After selecting by’Y’maze and cure, the qualified model rats divide into groups and cure by Tongluoxingnao effervescent tablet. After curing 90 days, rats should be evaluated.2. Effectiveness Study After the medicine curing, using Morris water maze, to evaluate the influence of Tongluoxingnao effervescent tablet on the ability of spatial learning and memory in model rat;Using HE staining method, To observe the effect of tongluoxingnao effervescent tablet on hippocampus pathomorphology; Using Immunohistochemistry and image analysis technique,to detect the effect of tongluoxingnao effervescent tablet on the expression of S YP in hippocampus. Comprehensive evaluate the effect on learning and memory of MID model rat.3.Study on brain energy metabolism Using the method of ELISA, to detect the content effect of Tongluoxingnao effervescent tablet in serum NOS and VEGF;Using automatic blood rheometer to blood viscosity in model rats,Comprehensive evaluate the effect of Tongluoxingnao effervescent tablet on brain blood supply;Using Immunohistochemistry and image analysis technique,to detect the effect of tongluoxingnao effervescent tablet on the expression of GLUT-1, MCT-1, MCT-2 and LDH-5 in hippocampus.evaluation of the influence of tongluoxingnao effervescent on energy substrate transporter. Determination of the content of ATP in cerebral cortex by HPLC method,to evaluate the effects of tongluoxingnao effervescent tablets on brain energy generation.Result:1.Effects of Tongluoxingnao effervescent tablets on learning and memory function of MID ratsPlace navigation trial showing,the training 2nd day to the training 5th day,The escape latency of the model group compared with the sham operation group was significantly prolonged with Statistical significance(P<0.05);After the training 3rd day,the drug groups are significantly shorter than the model group(P<0.05),especially in 5th day high, medium and low dose group are shorter significantly. Spatial probe trial showing,the model group compared with the sham operation group,the entering frequency of escape platform and the entering frequency of effective area are reduced remarkably; while the movement time of effective area and the middle ring residence time are shorter remarkably with statistical significance (P＜0.05).2.Effects on hippocampus pathological morphologyCompared with the sham operation group, Model control group rats hippocampal appear abnormal morphology appearing the number of cells decreased,nerve cell edema, intercellular visible brown fine particles, a large number of glial cells appeared;the focal brain tissue level confusion,the gray and white matter boundary unclear,nerve fibers from transverse staggered confusion,pathomorphism score significantly higher(P<0.05).Compared with the model control group, Tongluoxingnao effervescent tablets could significantly against the pathological morphological changes caused by MID and pathomorphism score significantly reduced with statistical significance (P＜0.05).3.Effects on SYP expressionCompared with the sham operation group,Model control group are significantly lower expression of SYP on positive immune reaction products and mean optical density are significantly lower with statistical significance (P＜0.05). While its treatment groups are significantly increased(P<0.05).4.Effects on blood rheology and blood vessel functionCompared with model control group,in the 4 shear rate of 1S-1,5S-1,30S-1 and 200S-1, Blood viscosity of Tongluoxingnao effervescent tablets group are significant reduction.Compared with model control group,the content of NOS and VEGF are significant reduction in serumTongluoxingnao effervescent tablets group.5.Effects on energy substrate transport-related proteinsCompared with the sham operation group, the expression of GLUT-1,MCT-1 and MCT-2 in hippocampus of model control group are significantly lower and mean optical density are significantly lower with statistical significance (P<0.05).While LDH-5 are significantly higher expression.Compared with model control group, Tongluoxingnao effervescent tablets could increase the expression of GLUT-1, MCT-1and MCT-2 and heighten mean optical density;decrease the expression of LDH-5 and drop mean optical density with statistical significance(P<0.05).6.Effects on the content of ATP in brainCompared with the sham operation group,Model control group ATP content in brain tissue was significantly reduced;Compared with model control group, Tongluoxingnao effervescent tablets increase ATP content in brain tissue with statistical significance (P＜0.05).Conclusion:Tongluoxingnao effervescent tablets intervention can improve MID rats’ learning-memory ability,cerebral morphology and the expression of SYP. Reduce blood viscosity and the content of serum NOS and VEGF;Promote the expression of brain tissue of GLUT-1,MCT-1 and MCT-2 and inhibit the expression of LDH-5;promote the brain tissue ATP generation.Through improving peripheral vascular function and reduce blood viscosity to promote energy substrate to the brain,which were transport by different transporters and promote the brain tissue ATP generation to improve synaptic function, Tongluoxingnao effervescent tablets could improve learning and memory function. |
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