安五脂素改善小鼠学习记忆障碍与抑制凋亡的作用

Anwulignan Improves learning and memory impairment and anti-apoptosic effect in D-galactose-induced mice

目的:观察安五脂素对D-半乳糖诱导的小鼠学习记忆障碍的改善作用并探讨其与凋亡相关机制。方法:选取雄性ICR小鼠,随机分为5组,即空白组(灌服羧甲基纤维素钠溶液,皮下注射生理盐水),模型组(灌服羧甲基纤维素钠溶液,皮下注射220 mg/kg D-半乳糖),安五脂素低、中、高剂量组(分别灌服1、2、4 mg/kg安五脂素,皮下注射220 mg/kg D-半乳糖)。连续给药42 d,1次/d。通过跳台实验观察分析小鼠学习记忆能力。行为学实验结束后,应用Western印迹法检测小鼠脑海马组织凋亡相关基因P53、Bcl2、Bax及Caspase3的表达情况。结果:与空白组比较,模型组小鼠跳台潜伏期显著缩短,错误次数显著增多(P<0.01),脑海马组织P53及Caspase3表达水平显著升高(P<0.05或P<0.01),Bcl2/Bax比值显著降低(P<0.05或P<0.01);而与模型组比较,安五脂素给药组小鼠跳台潜伏期显著延长,错误次数显著减少(P<0.01),脑海马组织P53及Caspase3表达水平显著降低(P<0.05或P<0.01),Bcl2/Bax比值显著升高(P<0.05或P<0.01)。结论:安五脂素能够改善D-半乳糖诱导的小鼠学习记忆障碍,该作用可能与其抑制小鼠脑海马组织细胞凋亡有关。

Objective To investigate the effects of anwulignan on D-galactose-induced learning and memory impairment in mice and its relation to apoptosis.Method Male ICR mice were randomly divided into 5 groups,namely,control group(gavage of sodium carboxymethyl cellulose solution,subcutaneous injection of normal saline),model group(gavage of sodium carboxymethyl cellulose solution,subcutaneous injection of 220 mg/kg D-galactose),and low,medium and high dose group(gavage of 1,2,and 4 mg/kg of anwulignan,subcutaneous injection of 220 mg/kg D-galactose).All mice were administered continuously for 42 days,once a day.The learning and memory abilities of mice were analyzed with step-down tests.After the behavioral experiment,the expressions of apoptosis-related gene P53,Bcl2,Bax and Caspase3 in mouse brain hippocampus tissue were detected.Results Compared with the control group,in the model group,the latency of step-down significantly decreased,observed by step-down and Morris water maze tests.After the behavioral tests,the expression of apoptosis-related genes P53,Bcl2,Bax and Caspase3 was detected by Western blot.Results The step-down the number of errors increased significantly(P<0.01),the hippocampus tissue P53 and Caspase3 expression levels increased significantly(P<0.05 or P<0.01),and the Bcl2/Bax ratio decreased significantly(P<0.05 or 0.01).However,compared with the model group,in anwulignan group,the latency of step-down significantly prolonged,the number of errors decreased significantly(P<0.01),the hippocampus tissue P53 and Caspase3 expression levels decreased significantly(P<0.05 or 0.01),and the Bcl2/Bax ratio increased significantly(P<0.05 or 0.01).Conclusion Anwulignan can improve the learning and memory impairment induced by D-galactose in mice,which may be related to its inhibition of apoptosis in the hippocampus cells of mice.