The Effect Of Vascular Endothelial Growth Factor To Forward Neural Behavior And Hippocampal Apoptosis Induced By Pubertal Status Epilepticus

Purpose: To research the effect of vascular endothelial growth factor(VEGF) to the long-term behavior、morphology、expression of apoptosis proteins Bax、Bcl-2 and the number of tunel positive cells in pubertal status epilepticus rats. Thus to know VEGF nerve protective effect.Methods: Forty eight old healthy SD rats were randomly divided into blank Control group, SE group, drug intervention group, and the drug intervention group was divided into PBS intervention group、VEGF intervention 1(VEGF0.02μg)、VEGF intervention 2(VEGF0.04μg) and VEGF intervention 3(VEGF0.06μg), each group has eight SD rats. Stereotactic apparatus was used to inject PBS or VEGF to the right ventricle. SE group and drug intervention group was induced SE by KA the next day. Open-field test、Balance beam test and Morris water maze test were taken at postnatal 50d、55d and 59 d respectively, and then to take Hematoxylin-eosin(HE) staining and immunohistochemical to detect the expression of Bax and Bcl-2 and the number of tunel positive cells of hippocampal CA3 cells.Results: 1. Behavioral results :( 1) Open-field test: Central residence time prolonged and the number of crossing squares increased obviously in SE group than that in Control group(P <0.01),VEGF intervention group1、2 and 3 could improve the situation(P<0.01).(2)Balance beam test: The balance beam mean score was significantly lower in SE group than that in Control group(P<0.01), VEGF intervention groups could increase the balance beam score(P < 0.01).(3)Morris water maze test:1 Incubation period stage: after 5 days navigation test, escape latency time in SE group rats was longer at D3 and D4 than that in Control group(P < 0.05),and the escape latency time was longer at D5 significantly than that in Control group(P<0.01), especially in VEGF intervention group 2(P<0.01). 2 The frequency of through the platform: The frequency of through the platform within 60 s in SE group was obviously lower than that in Control group(P<0.05), VEGF group could increase the frequency of through the platform within 60s(P<0.05), especially in VEGF intervention group 2(P<0.01).2. Hippocampal tissue pathological changes:the neurons in hippocampal CA3 area were observed arrangement rule, abundant cytoplasm and bigger nucleus in Control group, and the neurons in hippocampal CA3 area were visibled the cell volume decreased significantly、cell arrangement was sparse,intercellular space increased,cell body was irregular,cells swelled significantly and neuron degeneration and death were also visibled in SE group.VEGF intervention group could reduce neuronal degeneration and death, especially in VEGF intervention group 2.3. Immunohistochemical study of Bax and Bcl-2 in rat hippocampal neurons:(1) Bax positive cells of rats hippocampal neurons were visized a small amount of weak staining and scattered in the Control group, Bax positive cells distribution were relatively dense and positive cells AOD of rats hippocampal neurons enhanced in SE group(P<0.05); AOD of Bax positive cells distributed more intensively that in PBS intervention group(P<0.05),and AOD of Bax positive cells reduced significantly in VEGF intervention group 2(P<0.01).(2)Bcl-2 positive cells of rats hippocampal neurons were visized a small amount of weak staining and scattered in the Control group, the Bcl-2 distribution of positive cells of rats hippocampal neurons in SE group are decreased significantly than that in Control group(P<0.05) and AOD of Bcl-2 positive cells of rats hippocampal neurons increased significantly in VEGF intervention group 2(P<0.01).4. TUNEL test:The number of apoptosis neurons in hippocampal CA3 area of adulthood status epilepticus rats increased obviously than that in Control group, VEGF intervention groups could reduce the number of apoptosis neurons(P<0.05),especially in VEGF intervention group 1(P<0.01).Conclusion(1) SE could be induced by KA in puberty SD rats and generated a certain amount of brain damage and affected the forward behavior development and learning and memory.(2)VEGF could improve morphology of hippocampus neurons in the SE rats and develop its nerve protective effect by raising the expression of Bcl-2、reducing the expression of bax and reducing the number of Tunel positive cells.