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目的:研究人脑皮层锥体神经元Na~+电流的急性缺氧反应特征以及白藜芦醇(resveratrol,RES)对Na~+电流缺氧反应的影响。方法:采用全细胞膜片钳记录法,在人脑皮层脑片上记录锥体神经元对TTX敏感的电压依赖性Na~+电流,观察急性缺氧和白藜芦醇对Na~+电流幅值和激活性质的影响。结果:(1)急性缺氧使人脑皮层脑片上的锥体神经元Na~+电流呈现短暂的小幅增大后,出现长时程抑制(P<0.05),并使Na~+电流的I-V曲线左移(向超极化方向漂移)。(2)AMPA受体阻断剂NBQX阻断了缺氧引起的Na~+电流短暂增大(P<0.01),并加剧了Na~+电流的缺氧后抑制(P<0.01);GABA_A受体阻断剂Bicuculline对Na~+电流的缺氧性增大和缺氧后抑制无显著性影响(P>0.05);二者对缺氧引起的Na~+电流I-V曲线左移均无显著影响。(3)50μmol/L白藜芦醇阻断了Na~+电流的缺氧性增大(P<0.01),增强了Na~+电流的缺氧后抑制(P<0.05);100μmol/L白藜芦醇显著延迟了Na~+电流的缺氧性反应,使Na~+电流的缺氧性增大现象消失,并使Na~+电流的缺氧后抑制现象衰减(P<0.05)。50μmol/L和100μmol/L白藜芦醇均使Na~+电流激活曲线右移,接近正常。结论:人脑皮层锥体神经元Na~+电流对急性缺氧的反应主要表现为长时程抑制;AMPA受体活动可影响Na~+通道对急性缺氧的反应。白藜芦醇对人脑皮层锥体神经元Na~+电流缺氧反应的调节作用与剂量有关,小剂量可模拟NBQX的作用,而大剂量可降低Na~+通道对低氧的敏感性。
AIM: To investigate the characteristics of acute hypoxia response of Na ~ + currents in human cortical pyramidal neurons and the effect of resveratrol (RES) on Na + current hypoxia. Methods: Whole-cell patch-clamp recording method was used to record voltage-dependent Na ~ + current of pyramidal neurons in human brain cortical neurons. The effects of acute hypoxia and resveratrol on Na ~ + current amplitude and The nature of activation. Results: (1) Acute hypoxia induced long-term inhibition (P <0.05) of Na ~ + current in human cerebra cortex after short transient increase Curves left (drift to hyperpolarizations). (2) AMPA receptor antagonist NBQX blocked transient increase of Na + current induced by hypoxia (P <0.01) and aggravated Na + current hypoxia inhibition (P <0.01). GABA_A receptor Body blocker Bicuculline had no significant effect on hypoxia of Na ~ + current and inhibition after hypoxia (P> 0.05). Both of them had no significant effect on the left shift of IV curve caused by hypoxia. (3) 50μmol / L resveratrol blocked the increase of hypoxia in Na ~ + current (P <0.01), enhanced Na + current hypoxia inhibited (P <0.05) Resveratrol significantly delayed the hypoxia response of Na ~ + current, which resulted in the disappearance of the anoxia in Na ~ + current and the attenuation of Na ~ + current after hypoxia (P <0.05). Both the 50μmol / L and 100μmol / L resveratrol shifted the Na ~ + current activation curve to the right, close to normal. CONCLUSION: Na + currents in human cortical pyramidal neurons are mainly manifested as long-term depression in response to acute hypoxia. AMPA receptor activity may affect Na ~ + channel response to acute hypoxia. The effect of resveratrol on the Na ~ + current hypoxia response in human cortical neurons was dose-dependent. Low dose could simulate the effect of NBQX, while high dose could reduce the sensitivity of Na ~ + channel to hypoxia.