Effect Of Naotong Decoction On The Behavior Of VD Rats And The Key Factors Of Neurovascular Elements In Hippocampus CA1 Region

Objective To investigate the ability of learning and memory in vascular dementia model rats; The hippocampus area microvessel density (MVD) and sum area of lumens changes; The pathological tissue morphology, and the changes of antiapoptotic proteins the Bcl-2, apoptosis proteins Bax, intercellular adhesion molecule1(ICAM-1), endothelial barrier antigen (EBA),glial fibers acidic protein (GFAP) expression of hippocampal CAl area; And analyze the changes and the effect of Naotong decoction.Methods Ninety Sprague Dawley rats were randomly divided into six groups:â‘ pseudo-operation groupâ‘¡model groupâ‘¢Donepezil HCL groupâ‘£Naotong decoction high dose group(5)Naotong decoction moderate dose groupâ‘¥Naotong decoction low dose group, Fifteen rats contained in each group. Model making was performed on the rats in the last five groups by modified Pulsinelli4vascular occlusions method (4V0) after they were approved qualified by Morris Water Maze test. One week after the surgery, the rats underwent gavage treatment for4weeks, one time a day. After the treatment, the Morris Water Maze were used to test the ability of learning and memory in vascular dementia model rats, Immunohistochemical method to detect the hippocampus area microvascular density (MVD) and sum area of lumens changes, HE staining observation of hippocampal CAl area pathological tissue morphology, Immunohistochemical method to detect the Bcl-2, Bax, ICAM-1, EBA, GFAP protein expression in hippocampal CAl area, and computing the Bcl-2/Bax proportion.Results Compared to model group, escape time were shortened and the times of spanning the previous platform were increased in the high dose and moderate dose groups (P<0.01,P<0.05), there has no statistical difference compared to Donepezil HCL group. Compared to model group, the high dose and moderate dose groups hippocampal CAl pyramidal cells arranged a neat, level is clear, round or oval nucleus and nucleolus is clear, Chromatin rich, rare pyknotic degeneration of neurons, hippocampal structure is normal, normal neuron significantly increased in the hippocampus CA1area pathological tissue morphology. The high dose and moderate dose groups can obviously heighten the microvessel density (MVD) and sum area of lumens, increase newly born microvessel and promote the establishment of collateral circulation in hippocampal area, compared with model group and Donepezil HCL group with a statistically significant (P<0.01, P<0.05). The high dose and moderate dose groups can improve the Bcl-2expression and reduce the expression of Bax, improve the Bcl-2/Bax proportion, there are statistical difference compared with model grou(P<0.01, P<0.05). Compared with Donepezil group, Bcl-2expression increased, Bax expression is reduced and the Bcl-2/Bax ratio increased in the high dose group. The high dose and moderate dose groups can obviously improve the endothelial barrier antigen (EBA) expression, reduce the cell adhesion molecules (ICAM-1) expression, compared with model group with a significant difference(P<0.01). Compared with Donepezil HCL group, the EBA expression were improved and the expression of ICAM-1were decreased in the high dose group(P<0.01, P<0.05). The high dose and moderate dose groups can obviously reduce the GFAP expression, compared with the model group had significant difference (P<0.01); Compared with donepezil HCL group, the high dose group GFAP expression were increased but no statistical difference.Conclusion VD model established by modified Pulsinelli4vascular occlusions method had an impairment of learning and memory, reflecting that this model can be used as animal model of vascular dementia. Escape time and times of spanning previous platform were the classical indexes of Morris Water Maze with a certain sensitivity, can objectively reflect the change in learning and memory ability of animals and the efficacy of different drugs. The improvement of learning and memory ability in both high dose group and moderate group was related to Naotong decoction can promote ischemic angiogenesis and the establishment of collateral circulation, intervention to the important factor of NVU on the molecular biological mechanism, thus reduce the hippocampus CA1pyramidal cell injury and apoptosis, improve NVU overall function.