目的观察葛根素对血管性痴呆(VD)大鼠行为学、颞叶沉默信息调节因子3(SIRT3)表达及细胞凋亡的影响,并探讨其可能机制。方法采用大鼠双侧颈总动脉(CCA)永久性阻断法(2-VO)建立VD大鼠模型,大鼠随机分为假手术组、2.VO组和葛根素组,各组大鼠又分为4、8W2个时间点。应用Y型水迷宫实验测定动物的学习记忆能力,并应用免疫组织化学法、原位末端标记法(TUNEL)检测大鼠颞叶SIRT3蛋白表达水平及凋亡细胞数。结果2-VO组和葛根素组大鼠游全程时间和误入盲端次数均显著增加(P均〈0.05),但各时间点葛根素组大鼠的学习记忆成绩均显著优于2-VO组(P均〈0.05)。2-VO组和葛根素组大鼠颞叶SIR33的表达水平及凋亡细胞数均较假手术组明显增高(P均〈0.05),葛根素组SIRq3的表达水平较2-VO组明显增高,而凋亡细胞数较2-VO组明显减少(P均〈0.05)。结论葛根素可能通过上调SIRT3表达及抑制颞叶细胞凋亡改善VD大鼠学习记}乙能力。
Objective To observe the effects of puerarin on behavior, expression of silent information regulation 2 homolog 3 and apoptosis in temporal lobe of rats with vascular dementia and to investigate its possible mechanisms. Methods Rats of experimental groups were treated with a permanent bilateral common carotid arteries (CCA) occlusion (2-VO) to establish vascular dementia model. Male SD rats were randomly divided into three groups:sham-operated group, 2-VO group and puerarin group. Rats were evaluated on learning-memory ability by Y-type water maze test. At corresponding two time points of 4th week and 8th week respectively ,the dynamic changes on the cell counts of SIRT3 and apoptosis in temporal lobe were determined by immunohistochemical method and TUNEL, respectively. Results The swimming time and err times of rats in 2-~O group and puerarin group were significantly increased ( all P 〈 0.05), but at both time points the rats in puerarin group showed better perfornance than those in 2-VO group ( all P 〈 0.05 ). In both of 2-VO group and puer- arin group,the number of SIRT3 and TUNEL positive cells in temporal lobe were much more than that in sham-operated group (all P 〈 0.05). The expression of SIRT3 in puerarin group was obviously more than that in 2-VO group ( all P 〈 0.05) ,while TUNEL positive cells in puerarin group were distinctly less than those in 2-VO group ( all P 〈 0. 05 ). Conclusion Puerarin can inhibit apoptosis through upregulating the expression of SIRT3 protein in temporal lobe. Puerarin may improve cognitive ability in vascular dementia rats.