CAJ | 학술논문

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 ca?rotid 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7 d，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。
목적：탐토전렬선소E1（prostaglandin E1，PGE1）대쌍측경총동맥영구성결찰（bilateral common ca?rotid artery occlusion, BCCAO）대서학습기억공능급해마VEGF、BDNF표체적영향。방법48지대서수궤분위PGE1치료조（PGE1,10μg·kg-1·d-1,iv）、PGE1+VEGFR길항제조(PGE1,10μg·kg-1·d-1,iv；SU5416,25 mg·kg-1·d-1, ip)、용제대조조、가수술조，매조12지。술후15 d진행인지공능장애사선실험，24 d급여상응약물련속주사7 d，약물처리후2 d여Morris수미궁실험평고대서학습기억공능후처사，단백인적법관찰대서해마조직VEGF、BDNF적표체。결과여용제대조조급PGE1+VEGFR길항제조비，PGE1치료조평균잠복기강저（P<0.05），천월차수증다（5.77±0.83 vs.2.88±0.47 vs.2.63±0.44，P<0.01），차원평태상한정류시간백분비증대（32.28%±4.56%vs.20.42%±5.50%vs.23.08%±5.06%，P<0.05）；여용제대조조、가수술조상비，PGE1치료증가료해마VEGF표체량（0.057±0.005 vs.0.038±0.002 vs.0.027±0.002，P<0.05）、BDNF표체량（0.481±0.049 vs.0.339±0.021 vs.0.224±0.04，P<0.05）；여PGE1+VEGFR길항제조비，PGE1치료조VEGF표체량차이불명현（0.057±0.005 vs.0.053±0.003, P>0.05），단BDNF표체량증다（0.481±0.049 vs.0.373±0.034，P<0.05）。결론 PGE1가상조혈관성치태대서해마조직VEGF、BDNF적표체병가개선혈관성치태대서학습기억공능，이VEGFR길항제칙가부분길항PGE1적저일작용。
Objective To 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. Methods Forty-eight rats were randomly divided into PGE1 group (10μg·kg-1·d-1, iv), PGE1+VEGFR antagonist group (PGE1, 10μg·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 opera?tion. Half of the rats in each group were sacrificed for Western Blot at 6 days after MWM test. Western Blot was conduct?ed to examine the relative expression levels of VEGF and BDNF in the hippocampus. Results Compared 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 aug?ment of BDNF in PGE1 group was remarkable (0.481±0.049 vs. 0.373±0.034, P<0.05). Conclusions PGE1 can upregu?late 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.