肾脑复元汤对阿尔茨海默病模型大鼠学习记忆及凋亡相关蛋白的影响

Impacts of Shennao Fuyuan Decoction on Learning Memory and Apoptosis Related Proteins in the Rat Models of Alzheimer's Disease

目的观察肾脑复元汤对阿尔茨海默病(AD)模型大鼠的学习记忆能力及脑内海马神经元凋亡相关蛋白(Bcl-2和Caspase-3)表达的影响。方法将50只SPF级大鼠随机分为假手术组,模型组,肾脑复元汤高、中、低剂量组,每组10只。除假手术组外,其余各组均采用立体定向仪将β淀粉样蛋白(Aβ)25-35注入双侧脑室制备AD大鼠模型。造模后24 h,假手术组、模型组予蒸馏水灌胃,肾脑复元汤高、中、低剂量组予23.2 g/kg、11.6 g/kg、5.8 g/kg剂量肾脑复元汤灌胃。采用Morris水迷宫检测大鼠的学习记忆功能,Western Blot方法观察大鼠海马神经元Bcl-2和Caspase-3蛋白表达情况。结果模型组大鼠在5 d逃避潜伏期,后3 d逃避潜伏期时间均明显延长,大鼠跨越原平台位置的次数明显减少,Caspase-3表达明显升高,Bcl-2表达明显降低,与假手术组比较,差异有统计学意义(P<0.01)。经肾脑复元汤治疗后,肾脑复元汤各剂量组大鼠在5 d逃避潜伏期和后3 d逃避潜伏期的时间均明显缩短,而大鼠跨越原平台位置的次数明显增多,Caspase-3表达显著下降,Bcl-2表达显著升高,与模型组比较,差异有统计学意义(P<0.01)。结论肾脑复元汤能通过增强受损海马神经元Bcl-2的表达及抑制Caspase-3的表达,对海马神经元有抑制凋亡作用,可改善AD大鼠学习记忆能力。

Objective To observe the impacts of shennao fuyuan decoction on learning and memory ability and apoptosis related proteins（ Bcl-2 and Caspase-3） in the rat models of Alzheimer＇ s disease（ AD）. Methods Fifty SPF rats were randomized into a pseudo-operation group,a model group,the high-dose,middle-dose and low-dose groups of shennao fuyuan tang,10 rats in each one. Except the pseudo-operation group,the stereotaxic apparatus was used to inject（ Aβ）25-35 to bilateral ventricles for AD model preparation. In 24 h of modeling,the lavage with distilled water was used in the pseudo-operation group and the model group. The lavage with shennao fuyuan decoction,at 23. 2 g/kg,11. 6 g/kg and 5. 8 g/kg were used in the high-dose group,middle-dose group and low-dose group separately. The Morris water maze test was used to test the learning and memory of rats. Western blot method was used to observe the levels of Bcl-2 and Caspase-3 in hippocampal neuron. Results In the model group,the escape latent time in 5days and the last 3 days was prolonged apparently. The frequency of over-jumping the flat was reduced apparently. Caspase-3 expression was increased apparently and Bcl-2 decreased apparently,indicating the significant differences as compared with the pseudo-operation group（ P〈 0. 01）. After treatment with shennao fuyuan decoction,at each dose group,the escape latent time in 5 days and the last 3 days was shortened apparently,the frequency of over-jumping the flat was increased apparently. Caspase-3 expression was reduced significantly and Bcl-2 increased significantly,indicating the significant differences as compared withthe model group（ P〈 0. 01）. Conclusion Shennao fuyuan decoction improves the learning and memory ability of AD rats by increasing the expression of Bcl-2 and inhibiting the expression of Caspase-3 in the injured hippocampal neuron and acting on the inhibition of hippocampal apoptosis.