CAJ | 학술논문

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.
목적 관찰응용정분태대혈관성치태대서인지공능、해마세포조망급p38MAPK린산화적영향,이탐토기궤제.방법 용량혈관법(2VO)건립혈관성치태(VD)모형.장60지3월령웅성Wistar대서수궤분성VD모형조、가수술조화정분태조.정분태조급여120 mg·kg-1·d-1적정분태용액2 ml관위,VD조화가수술조급여등량적2 ml식물유관위,1월후응용Morris수미궁실험분별측시각조대서적학습기억능력,TUNEL법검측해마CA1구세포조망,단백인적(Westem blot)법관찰대서해마구p38MAPK린산화변화.결과 전3d정분태조은폐평태도피잠복기[분별위(48.72±7.01)s,(42.41 ±4.06)s,(40.34±2.46)s],명현소우모형조은폐평태도피잠복기[(82.71±8.27)s,(80.36±9.65)s,(77.74±6.33)s],차이유통계학의의(P＜0.01);정분태조원평태상한시간、천월원평태차수[(26.45±4.66)s,(1.84±0.82)차],대우모형조원평태상한시간、천월원평태차수[(18.67±5.39)s,(1.32±0.61)차],차이유통계학의의(P＜0.01).대서해마구세포조망、린산화p38MAPK적표체(p-p38MAPK/β-action광밀도치)적비교:정분태조분별위[(153.65±9.85)개,(0.42±0.04)],명현저우VD모형조[(209.46± 11.49)개,(0.88±0.10)],차이유통계학의의(P＜0.01).결론 정분태능현저개선VD대서적학습기억능력,가능시통과억제p38MAPK통로,진일보억제해마구세포조망이실현적,저가능시정분태치료혈관성치태적작용궤제지일.
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.