丁苯酞对血管性痴呆大鼠认知功能及海马细胞凋亡、磷酸化p38MAPK表达的影响

Effects of butylphthalide on cognitive function, apoptosis and p-p38MAPK expression in hippocampus of rat model of vascular dementia

目的 观察应用丁苯酞对血管性痴呆大鼠认知功能、海马细胞凋亡及p38MAPK磷酸化的影响,以探讨其机制.方法 用两血管法（2VO）建立血管性痴呆（VD）模型.将60只3月龄雄性Wistar大鼠随机分成VD模型组、假手术组和丁苯酞组.丁苯酞组给予120 mg·kg-1·d-1的丁苯酞溶液2 ml灌胃,VD组和假手术组给予等量的2 ml植物油灌胃,1月后应用Morris水迷宫实验分别测试各组大鼠的学习记忆能力,TUNEL法检测海马CA1区细胞凋亡,蛋白印迹（Westem blot）法观察大鼠海马区p38MAPK磷酸化变化.结果 前3d丁苯酞组隐蔽平台逃避潜伏期[分别为（48.72±7.01）s,（42.41 ±4.06）s,（40.34±2.46）s],明显小于模型组隐蔽平台逃避潜伏期[（82.71±8.27）s,（80.36±9.65）s,（77.74±6.33）s],差异有统计学意义（P＜0.01）;丁苯酞组原平台象限时间、穿越原平台次数[（26.45±4.66）s,（1.84±0.82）次],大于模型组原平台象限时间、穿越原平台次数[（18.67±5.39）s,（1.32±0.61）次],差异有统计学意义（P＜0.01）.大鼠海马区细胞凋亡、磷酸化p38MAPK的表达（p-p38MAPK/β-action光密度值）的比较：丁苯酞组分别为[（153.65±9.85）个,（0.42±0.04）],明显低于VD模型组[（209.46± 11.49）个,（0.88±0.10）],差异有统计学意义（P＜0.01）.结论 丁苯酞能显著改善VD大鼠的学习记忆能力,可能是通过抑制p38MAPK通路,进一步抑制海马区细胞凋亡而实现的,这可能是丁苯酞治疗血管性痴呆的作用机制之一.

Objective To study the effects of butylphthalide on cognitive function,apoptosis and pp38MAPK in hippocampus of rat model of vascular dementia.Methods The vascular dementia （VD） model was established by two vascular （2VO） method,and then sixty male Wistar rats were randomly divided into VD group,sham operation group and NBP （butylphthalide） group.Rats in NBP group were given 120 mg · kg-1 · day-1 dose butylphthalide by gavage,and rats in VD group and sham operation group were given the same dose vegetable oil.The cognitive function of each rat was tested by Morris water maze.The expression of p-p38MAPK in the hippocampus was observed by Western blot;and the apoptosis was observed in hippocampal CAl region by TUNEL staining.Results The hidden platform escape latency of NBP group （（48.72 ± 7.01） s,（42.41 ± 4.06） s,（40.34 ± 2.46） s）was significantly shortened compared with those of VD group（（82.71±8.27） s,（80.36±9.65） s,（77.74±6.33） s）（P〈 0.01） ; and the former platform quadrant time and the number of passing through the platform of NBP group （（26.45±4.66）s,（1.84±0.82） times） were significantly prolonged （P〈0.01） compared with those of VD group （（18.67±5.39） s,（1.32±0.61） times）;the apoptosis and the expression of p38MAPK phosphorylation in hippocampus in NBP group （（153.65±9.85）,（0.42±0.04）） significantly reduced （P〈0.01） compared with those of VD group （（209.46±11.49）,（0.88±0.10））.Conclusion Butylphthalide can improve the learning and memory ability of VD rats,the reduce apoptosis in the hippocampus by the inhibition of the P38MAPK pathway.This may be one of the ways by which butylphthalide can treat vascular dementia.