益肺宣肺降浊方通过影响脑源性神经营养因子改善血管痴呆记忆的作用机制

Yifei Xuanfei Jiangzhuo Formula Improves Memory in Vascular Dementia by Regulating Brain-derived Neurotrophic Factor

目的:探讨益肺宣肺降浊方及通过影响脑源性神经营养因子(BDNF)改善血管痴呆记忆的作用机制。方法:将Wistar大鼠随机分为假手术组,模型组,益肺宣肺降浊方低剂量组,益肺宣肺降浊方中剂量组,益肺宣肺降浊方高剂量组,石杉碱甲组,每组15只。其中除假手术组外均构建大脑中动脉栓塞法(MCAO)大鼠血管性痴呆模型。益肺宣肺降浊方低剂量组、中剂量组、高剂量组分别给予1.25、2.5、5 g/kg的益肺宣肺降浊方灌胃,假手术组和模型组给予同等体积的生理盐水灌胃,石杉碱甲组给予3 mg/kg的石杉碱甲灌胃。各组每日灌胃1次,持续给药4周后,进行Morris水迷宫试验检测动物神经行为学;Morris水迷宫结束后,获取大鼠海马组织,通过TUNEL染色检测海马组织细胞凋亡情况;用免疫组织化学检测海马组织中BDNF表达。结果:Morris水迷宫行为学结果显示,与模型组比较,不同剂量的益肺宣肺降浊方组的逃避潜伏期显著减少(P<0.05),穿越平台次数明显增加(P<0.05);TUNEL结果表明益肺宣肺降浊方可有效抑制海马神经元凋亡(P<0.05);免疫组织化学结果显示益肺宣肺降浊方显著上调大鼠海马组织中BDNF的表达(P<0.05)。结论:益肺宣肺降浊方可改善血管痴呆大鼠的学习和记忆功能障碍,其作用机制与抑制神经元凋亡和上调BDNF表达有关。

Objective:To investigate the role and mechanism of Yifei Xuanfei Jiangzhuo Formula in improving memory in vascular dementia by regulating brain-derived neurotrophic factor(BDNF).Methods:Wistar rats were randomly assigned into sham,model,and low-,medium-,high-dose(1.25,2.5,and 5 g/kg,respectively) Yifei Xuanfei Jiangzhuo Formula,and huperzine A(3 mg/kg) groups(n=15).The rats in other groups except the sham group were subjected to middle cerebral artery occlusion(MCAO) for the modeling of vascular dementia.The rats in the drug intervention groups were administrated with corresponding drugs by gavage,and those in the sham and model groups were administrated with the same volume of normal saline once a day for 4 weeks.Morris water maze test was performed to examine the neurobehaviors of the rats.After the test,the hippocampal tissue was collected,and the terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) was employed to detect apoptosis in the hippocampal tissue.The BDNF expression in the hippocampal tissue was determined by immunohistochemistry.Results:The results of Morris water maze test showed that compared with the model group,Yifei Xuanfei Jiangzhuo Formula shortened the escape latency(P<0.05) and increased the number of crossing the platform(P<0.05).The TUNEL results showed that Yifei Xuanfei Jiangzhuo Formula inhibited the apoptosis of hippocampal neurons(P<0.05).The immunohistochemical results showed that Yifei Xuanfei Jiangzhuo Formula up-regulated the BDNF expression in the hippocampal tissue(P<0.05).Conclusion:Yifei Xuanfei Jiangzhuo Formula can improve the learning and memory in the rat model of vascular dementia by inhibiting neuronal apoptosis and up-regulating BDNF expression.