前列腺素E1上调血管性痴呆大鼠海马组织VEGF、BDNF的表达

PGE1 alleviates cognitive impairment and upregulates the VEGF and BDNF expression in VD rats

目的探讨前列腺素E1(prostaglandin E1,PGE1)对双侧颈总动脉永久性结扎(bilateral common carotid artery occlusion,BCCAO)大鼠学习记忆功能及海马VEGF、BDNF表达的影响。方法 48只大鼠随机分为PGE1治疗组(PGE1,10μg·kg-1·d-1,iv)、PGE1+VEGFR拮抗剂组(PGE1,10μg·kg-1·d-1,iv;SU5416,25 mg·kg-1·d-1,ip)、溶剂对照组、假手术组,每组12只。术后15 d进行认知功能障碍筛选实验,24 d给予相应药物连续注射7d,药物处理后2 d予Morris水迷宫实验评估大鼠学习记忆功能后处死,蛋白印迹法观察大鼠海马组织VEGF、BDNF的表达。结果与溶剂对照组及PGE1+VEGFR拮抗剂组比,PGE1治疗组平均潜伏期降低(P<0.05),穿越次数增多(5.77±0.83 vs.2.88±0.47 vs.2.63±0.44,P<0.01),且原平台象限停留时间百分比增大(32.28%±4.56%vs.20.42%±5.50%vs.23.08%±5.06%,P<0.05);与溶剂对照组、假手术组相比,PGE1治疗增加了海马VEGF表达量(0.057±0.005 vs.0.038±0.002 vs.0.027±0.002,P<0.05)、BDNF表达量(0.481±0.049 vs.0.339±0.021 vs.0.224±0.04,P<0.05);与PGE1+VEGFR拮抗剂组比,PGE1治疗组VEGF表达量差异不明显(0.057±0.005 vs.0.053±0.003,P>0.05),但BDNF表达量增多(0.481±0.049 vs.0.373±0.034,P<0.05)。结论 PGE1可上调血管性痴呆大鼠海马组织VEGF、BDNF的表达并可改善血管性痴呆大鼠学习记忆功能,而VEGFR拮抗剂则可部分拮抗PGE1的这一作用。

ObjectiveTo explore the effect of PGE1 on the cognitive impairment and the expression of VEGF and BDNF in the hippocampus after bilateral common carotid artery occlusion in adult rats.MethodsForty-eight rats were randomly divided into PGE1 group(10 μg·kg-1·d-1,iv),PGE1+ VEGFR antagonist group(PGE1,10 μg·kg-1·d-1,iv;SU5416,25 mg·kg-1·d-1,ip),saline group and sham group(n=12 each).Morris Water Maze test(MWM) was used to examine cognitive function in rats.Drugs and saline were given to VD rats at 24 d for 7 consecutive days following operation.Half of the rats in each group were sacrificed for Western Blot at 6 days after MWM test.Western Blot was conducted to examine the relative expression levels of VEGF and BDNF in the hippocampus.ResultsCompared to saline and PGE1+ VEGFR antagonist groups,the escape latency in PGE1 group was shorter(P<0.05),and the times that rats swam across the platform location and time percentage in previous platform quadrant in PGE1 group was longer(5.77±0.83 vs.2.88±0.47 vs.2.63±0.44,P<0.01;32.28%±4.56% vs.20.42%±5.50%,23.08%±5.06%,P<0.05).Compared with saline group and sham group,PGE1 group had higher levels of VEGF(0.057±0.005 vs.0.038±0.002 vs.0.027±0.002,P<0.05)and BDNF(0.481±0.049 vs.0.339±0.021 vs.0.224±0.04,P<0.05).but the increase in VEGF expression in PGE1 group was no significant(0.057±0.005 vs.0.053±0.003,P>0.05) compared with PGE1+VEGFR antagonist group,while the augment of BDNF in PGE1 group was remarkable(0.481±0.049 vs.0.373±0.034,P<0.05).ConclusionsPGE1 can upregulate VEGF and BDNF expression and modify cognitive impairment in VD rats,while the effects of PGE1 on cognitive function and BDNF expression can be partially blocked by VEGFR antagonist SU5416.