β-淀粉肽-(1-40)对电压依赖性钙电流的作用及铝和银杏内酯B对该作用的影响  

Action and Mechanism of β-amyloid_(1-40) on VDCC and the Influence of Aluminum and Ginkgolide B on Its Action

作　　者：陈蕾[1] 刘长金[1] 唐明[1] 胡新武[1] 李爱[1] 张亮品[1] 骆红艳[1] 胡晓玲[1] 

机构地区：[1]华中科技大学同济医学院基础医学院生理学系,武汉430030

出　　处：《华中科技大学学报（医学版）》2004年第6期659-662,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的　探讨不同时期配制的 β 淀粉肽 (1 4 0 ) (Aβ1 40 )对大鼠海马CA1区锥体神经元高电压依赖性钙通道电流 (IHVA)的作用并观察铝和银杏内酯B (GB)对该作用的影响。方法　应用全细胞膜片钳技术记录海马神经元IHVA电流 ,并观察药物对其的作用。结果　 (1)细胞外给予老化处理的Aβ1 40 可以增强IHVA幅度 ,Aβ1 40 的作用具有不可逆性和浓度依赖性 ;新鲜配制的Aβ1 40 对IHVA几乎没有影响。 (2 )Aβ1 40 增强IHVA的作用可以被L 型钙通道阻断剂nifedipine抵消。 (3)PKA的抑制剂H 89可以抵消Aβ1 40 对IHVA的增强作用。 (4)Aβ1 40 增加IHVA的作用可被 1 0mmol/L的AlCl3 进一步增加。 (5 )细胞外给予GB对正常的IHVA没有影响 ,但可抵消Aβ1 40 对IHVA的增强作用。结论 β 淀粉肽(Aβ)通过增强IHVA可引起胞内钙超载 ,这可能是其产生神经毒性作用的机制之一 ,铝可以加强Aβ的毒性作用 ;GB可通过抑制钙离子内流对神经元起一定保护作用。Objective To investigate the effect of β-amyloid peptide 1 -40 (Aβ 1-40) on high voltage-dependent calcium current (I HVA) from acutely isolated hippocampal CA1 pyramidal neurons in rats and the influenc e of aluminum and ginkgolide B on the action of Aβ 1-40. Methods Whole cell patch clamp technique was used to record the I HVA in hippocampal CA1 pyramidal neurons.Results Aggregated Aβ 1-40 could inevitably increase the amplitude of I HVA in a dose-dependent manner; Fresh Aβ 1-40 almos t had no effect on I HVA. L-type of calcium channel antagonist nifedipine could abolish the increase of I HVA by Aβ 1-40. PKA antagonist H-89 could cancel the increase of I HVA by Aβ 1-40. 1 mmol/L AlCl 3 cou ld increase I HVA to a higher degree after Aβ 1-40 application. Gink golide B had no effect on I HVA in normal neurons, but could cancel the inc rease of I HVA by Aβ 1-40. Conclusion Aβ could lead to intracellular free calcium overloa d by increasing I HVA, which might be one of the reasons for its neurotoxic ity. Aluminum and Aβ 1-40 had synergistic action in neurotoxicity. Ginkgo lide B could prevent neurons from neurotoxicity by inhibiting calcium influx.

关 键 词：AΒ1-40 银杏内酯B 细胞外 增强作用 影响 依赖性 观察 增强 淀粉 配制 

分 类 号：R749[医药卫生—神经病学与精神病学] R338[医药卫生—临床医学]