补阳还五汤对AD大鼠β-APP及凋亡相关蛋白影响的实验研究
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摘要
本研究以AD发病理论“β-淀粉样蛋白级联假说”、“细胞凋亡学说”为切入点,以Aβ代谢途径参与AD发病为基础,采用Aβ_(1-40)海马区注射诱发大鼠脑内神经元损伤,复制AD模型大鼠。以β-淀粉样蛋白沉积、神经元损伤病变和细胞凋亡为治疗靶点,利用Morris水迷宫和神经病理学方法观察AD大鼠行为学及脑组织形态学变化;免疫组织化学法检测大鼠海马区Aβ1-40、β-APP、bcl-2/bax与caspase-3蛋白表达。从行为学、分子水平,探讨补阳还五汤对Aβ诱导的AD大鼠的治疗效果及相关机制,为其临床应用提供实验依据。
研究结果表明,补阳还五汤对Aβ_(1-40)所致AD模型大鼠学习记忆障碍具有明显改善作用;可显著地降低AD模型大鼠明显增高的海马Aβ沉积,改善Aβ所造成的神经元损害;可上调AD模型大鼠bcl-2的表达、bcl-2/bax的比率,下调bax、caspase-3的表达,抑制细胞凋亡。
补阳还五汤可能通过上调bcl-2的表达、bcl-2/bax的比率,下调bax、caspase-3的表达,抑制细胞凋亡,干预β-APP生成与代谢,合理地调控Aβ过度沉积引起的神经元凋亡、线粒体损伤,有效地减轻Aβ毒性作用所致脑组织神经元损伤,从而改善学习记忆障碍,起到防治AD的作用。
Starting from the theories of AD,the hypothesis of cell apoptosis and the hypothesis ofβ-amyloid protein cascades,and based on the metabolic pathway of Aβthat participates in AD,this experiment employed Aβ_(1-40)to inject the Hippocampus to induce neuronal damage in brain and to copy the AD Rat Subject.By the curative target ofβ-amyloid protein deposition and neuronal damage pathological changes and cell apoptosis,we adopted Morris water maze and neuropathology to observe the changes of ethology and brain histomorphology of AD Rat;adopted immunohistochemical approach to detect the expression of Aβ_(1-40),β-APP,bcl-2,bax,caspase-3 in Hippocampus of rat. Then we would from the ethology and molecule levels study the therapeutic efficacy and amynology mechanism of Buyang Huanwu Decoction for AD rat induced by Aβto provide experimental data for clinical application.
The results of the study indicated that Buyang Huanwu Decoction had greatly lessened the memorizing dificulties of AD Rat Subject brought about by Aβ;greatly lowered the highly increased Aβdeposition in Hippocampus and brain mantle;greatly lessened neuronal damage caused by Aβ;stepped up the expression of bcl-2 in Hippocampus of AD rat model;then could lower high expression of bax and caspase-3 in Hippocampus;finally stepped up bcl-2/bax'ratio,Repress cell apoptosis.
Buyang Huanwu Decoction was likely to,by the regulation of stepping up the expression of bcl-2,of lowering the high expression of Bax and caspase-3 and of stepping up bcl-2/bax'ratio,restrain cell apoptosis,interfere with the generation and metabolism ofβ-APP and control appropriately the cell apoptosis and mitochondrion damage caused by over deposition of Aβ. Accordingly,the decoction lessened the brain neuronal damage effectively caused by Aβtoxic effects and naturally relieved the memorizing difficulties and prevented AD.
研究结果表明,补阳还五汤对Aβ_(1-40)所致AD模型大鼠学习记忆障碍具有明显改善作用;可显著地降低AD模型大鼠明显增高的海马Aβ沉积,改善Aβ所造成的神经元损害;可上调AD模型大鼠bcl-2的表达、bcl-2/bax的比率,下调bax、caspase-3的表达,抑制细胞凋亡。
补阳还五汤可能通过上调bcl-2的表达、bcl-2/bax的比率,下调bax、caspase-3的表达,抑制细胞凋亡,干预β-APP生成与代谢,合理地调控Aβ过度沉积引起的神经元凋亡、线粒体损伤,有效地减轻Aβ毒性作用所致脑组织神经元损伤,从而改善学习记忆障碍,起到防治AD的作用。
Starting from the theories of AD,the hypothesis of cell apoptosis and the hypothesis ofβ-amyloid protein cascades,and based on the metabolic pathway of Aβthat participates in AD,this experiment employed Aβ_(1-40)to inject the Hippocampus to induce neuronal damage in brain and to copy the AD Rat Subject.By the curative target ofβ-amyloid protein deposition and neuronal damage pathological changes and cell apoptosis,we adopted Morris water maze and neuropathology to observe the changes of ethology and brain histomorphology of AD Rat;adopted immunohistochemical approach to detect the expression of Aβ_(1-40),β-APP,bcl-2,bax,caspase-3 in Hippocampus of rat. Then we would from the ethology and molecule levels study the therapeutic efficacy and amynology mechanism of Buyang Huanwu Decoction for AD rat induced by Aβto provide experimental data for clinical application.
The results of the study indicated that Buyang Huanwu Decoction had greatly lessened the memorizing dificulties of AD Rat Subject brought about by Aβ;greatly lowered the highly increased Aβdeposition in Hippocampus and brain mantle;greatly lessened neuronal damage caused by Aβ;stepped up the expression of bcl-2 in Hippocampus of AD rat model;then could lower high expression of bax and caspase-3 in Hippocampus;finally stepped up bcl-2/bax'ratio,Repress cell apoptosis.
Buyang Huanwu Decoction was likely to,by the regulation of stepping up the expression of bcl-2,of lowering the high expression of Bax and caspase-3 and of stepping up bcl-2/bax'ratio,restrain cell apoptosis,interfere with the generation and metabolism ofβ-APP and control appropriately the cell apoptosis and mitochondrion damage caused by over deposition of Aβ. Accordingly,the decoction lessened the brain neuronal damage effectively caused by Aβtoxic effects and naturally relieved the memorizing difficulties and prevented AD.
引文
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