目的研究肉苁蓉总苷(glycosides of cistanche,GCs)对血管性痴呆(vascular dementia,VD)模型大鼠行为学及海马脑区tau蛋白、p-tau蛋白、Aβ淀粉样蛋白表达的影响,探讨GCs对VD的防治作用。方法双侧颈总动脉结扎(2-VO法)建立VD大鼠模型,随机分为假手术组、VD模型组、GCs低、中、高剂量治疗组和药物对照共6组,Morris水迷宫实验评价各组大鼠的空间学习记忆能力;免疫组化方法检测海马脑区tau蛋白、p-tau蛋白、Aβ淀粉样蛋白表达量的改变。结果 (1)Mories水迷宫研究发现术后1 d、2 d、3 d、4 d、5 d VD组大鼠逃避潜伏期明显延长,与假手术组相比差异明显,有统计学意义(P〈0.01,P〈0.05);GCs治疗后,VD大鼠定位航行试验的逃避潜伏期显著缩短,有统计学意义(P〈0.01);但GCs中剂量组与药物对照组相比差异无统计学意义;(2)模型组大鼠海马脑区tau蛋白、P-tau蛋白、Aβ淀粉样蛋白表达量均显著上升;GCs治疗后,表达量显著下降,与模型组相比(P〈0.05),差异有统计学意义。结论 (1)本研究发现tau蛋白、p-tau蛋白、Aβ淀粉样蛋白表达量显著升高,推测VD发病过程与其他类型痴呆如AD存在共同的病理特征;(2)GCs通过减少VD大鼠海马脑区tau蛋白、p-tau蛋白、Aβ淀粉样蛋白表达,有效改善VD模型大鼠的认知功能。
Objective To observe the effect of glycosides( GCs) on learning and memory dysfunction,explore the prevention and cure function of GCs on vascular dementia( VD) rats model. Methods VD rats model was established by bilateral common carotid artery ligation( 2-VO); rats were divided into VD model group,sham-operation group,GCs low、middle、high dose treatment groups and drug control group; Spatial learning and memory ability of rats was detected by Mories water maze; and tau,P-tau,Aβ amyloid protein expression were investigated by immunohistochemistry. Results( 1)The Mories water maze experiment confirmed the escape latent period was obviously prolonged 1,2,3,4,5 day after the operation,which was significant different compared with the control group( P〈0. 01,P〈0. 05); but the escape latency significantly shortened after GCs treatment;( 2) tau,P-tau,Aβ amyloid protein expression in hippocampus of VD rat markedly increased compared with control group( P〈0. 05); and decreased after GCs treatment. Conclusion( 1) tau protein,p-tau protein,Aβ amyloid protein expression markedly increased by immunohistochemical study,and we speculate that VD with AD has common pathological characteristic in the process;( 2) GCs can decrease expression of tau protein,p-tau protein,Aβamyloid protein,so as to effectively improve the cognitive functions of VD model rats.