熟地黄抑制阿尔茨海默病样大鼠海马神经元凋亡的作用

Prepared Radix Rehmanniae protects hippocampcal neurons of rats with Alzheimer's-like disease from amyloid-β peptide1-40 induced apoptosis

目的探讨凋亡机制在β-淀粉样肽致阿尔茨海默病(AD)作用中的意义及熟地黄对Aβ神经毒的干预效果。方法用β-淀粉样肽1￣40片段(Aβ1-40)行大鼠侧脑室注射以建立AD样病变动物模型;用Morris水迷宫测试系统检测大鼠学习记忆功能;蛋白印记法及激酶活性测定法检测海马内半胱天冬氨酸蛋白酶-3(caspase-3)的表达和活性,琼脂糖凝胶电泳观察海马神经元凋亡;以熟地黄(大、小剂量)对Aβ1-40处理的大鼠连续灌胃21d,观察其干预效果。结果大鼠脑内注射Aβ1-40后,经行为学检测发现其学习记忆功能明显减退;海马内caspase-3含量和活性明显增高,细胞核DNA降解;经熟地黄灌胃处理后,对上述变化有不同程度的改善作用。结论Aβ1-40能诱导海马神经元凋亡,熟地黄对Aβ1-40诱导的大鼠海马神经元凋亡有保护作用,这可能是其改善AD样大鼠学习记忆功能作用机制之一。

Objective To investigate both the role of apoptosis in the pathogenesis of amyloid β-peptide1-40 （Aβ1-40） and the therapeutic effect of Prepared Radix Rehmanniae （PRR） on the neurotoxicity of Aβ1-40 in rat brains. Methods A 5μL volume of Aβ1-40 or vehicle was injected into the left lateral ventricle to establish an animal model with Alzheimer＇ s-like disease. Morris water maze tests were used for behavioral study. Western blot and kinase activity assess were used to determine the expression and activity of caspase-3 in the hippocampus. The hippocampal neuronal apoptosis was observed by DNA electrophoresis. Aβ1-40 injected rats were treated with PRR at a large or small dose for 21 consecutive days. Results Intracerebroventricular injection of Aβ1-40 induced a marked learning and memory dysfunction in Morris water maze tests. Apoptotic changes were detected in the hippocampus of Aβ1-40 injected rats, such as the increases of the concentration and activity of caspase-3, nucleus degeneration. After treatment with PRR [8, 4 g/（kg·d）, ig], the changes mentioned above were significantly improved. Conclusion Aβ1-40 could induce hippocampal neuronal apoptosis. PRR can remarkably inhibit the neuronal apoptosis. This may be one of the therapeutic mechanisms of PRR improving the impaired learning and memory induced by Aβ1-40 in rats.