紫苏提取物对D-半乳糖衰老小鼠学习记忆障碍的改善作用

Improving effect of Perilla frutescens extract on learning and memory impairment in subacute senile mice induced by D-galactose

目的观察紫苏乙酸乙酯提取物对D-半乳糖衰老模型小鼠学习记忆障碍的改善作用。方法 90只小鼠颈背部皮下注射D-半乳糖(1 g/kg)连续6周,建立亚急性衰老模型。造模的同时,各给药组分别灌胃相应药物(紫苏提取物:150,300,600 mg/kg;迷迭香酸:55,110,220 mg/kg;脑复康阳性对照:500 mg/kg)。42 d后采用跳台、Y迷宫、Morris水迷宫法测试小鼠学习记忆能力,检测小鼠脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)、一氧化氮合酶(NOS)、乙酰胆碱酯酶(AChE),对海马CA1区神经细胞形态学观察。结果紫苏提取物和迷迭香酸能明显改善D-半乳糖所致的衰老体征和自发活动减少,降低跳台错误次数,延长错误潜伏期(P<0.05,P<0.01),减少达到学会标准的训练次数(P<0.05);缩短逃避潜伏期,延长小鼠在安全台所在象限的游泳时间和游程,增加安全台穿越次数(P<0.05,P<0.01);并能有效地提高衰老小鼠脑SOD和GSH-Px(P<0.05,P<0.01),降低MDA、NO、NOS、AchE(P<0.05,P<0.01),呈量效依赖趋势,还能改善海马CA1区神经细胞受损状态。结论紫苏提取物和迷迭香酸能改善D-半乳糖衰老模型小鼠学习记忆障碍。其机制可能与清除自由基,抑制AchE活性,减少乙酰胆碱(Ach)水解,减轻NO对神经细胞的毒性有关。

AIM To study the improving effect of Perilla frutescens extract（PE）,extracted by ethyl acetate,on learning and memory impairment in subacute senile mice induced by D-galactose.METHODS Ninety mice were randomly divided into normal control group（NC）,model group,positive control group（pairacetam,500 mg/kg）,treated groups with PE（150,300,600 mg/kg）,and treated groups with rosmarinic acid（55,110,220 mg/kg） according to their body weights.Except NC group,all the other groups were subcutaneously injected with 1 g/（kg·d） D-galactose for 6 w,whereas NC group with normal saline.At the same time,the other groups were adminstered with corresponding drugs for successive 42 d.Then the learning and memory ability of mice were measured by step down test,Y-maze test and Morris water maze test.The activities of superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）,malondiadehyde（MDA）,nitric oxide（NO）,NO synthase（NOS） and acetylcholinesterase（AchE） in brain were detected.Morphology of hippocampal nerve cells were investigated.RESULTS Compared with the model group,PE and rosmarinic acid significantly improved aging sign and spontaneous activity,reduced error numbers,increased latent period and reduced training times（P〈0.05,P〈0.01）,decreased escape latency,increased swimming time and swimming distance in platform quadrant and times of crossing platform（P〈0.05,P〈0.01）.PE and rosmarinic acid could also increase the activities of SOD and GSH-Px（P〈0.05）,reduce AchE,NOS activity and MDA,NO level（P〈0.05,P〈0.01） with dose-dependent tendency,and prevent hippocampal nerve cells from damaging obviously.CONCLUSION PE and rosmarinic acid can significantly improve learning and memory ability in subacute senile mice induced by D-galactose.The mechanism may be related to scavenging free radicals,inhibiting activity of AchE,reducing hydrolysis of acetylcholine and decreasing toxicity of NO on nerve cells.