白藜芦醇对人脑皮层锥体神经元Na^+电流缺氧性变化的影响  

Effects of resveratrol on the hypoxic responses of Na^+ currents in human cortical pyramidal neurons

作　　者：陈静[1,2] 高大宽[3] 任颖鸽 成胜权[2] 张月萍[2] 杜永平[1] 费舟[3] 

机构地区：[1]第四军医大学西京医院全军中医内科中心,西安710032 [2]第四军医大学西京医院儿科脑发育研究室,西安710032 [3]第四军医大学西京医院全军神经外科研究所,西安710032

出　　处：《神经解剖学杂志》2016年第1期44-50,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(30871029);第四军医大学西京医院助推计划(XJZT10T07)

摘　　要：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。Objective ： To study the properties and effects of resveratrol （RES） on Na＋ currents of human cortical pyramidal neurons in response to acute hypoxia. Methods： Whole-cell patch-clamp technique was used to record the TTX-sensitive voltage-dependent Na＋ currents of pyramidal neurons in human cortical slices, in order to investigate the effects of acute hypoxia and resveratrol on Na ~ current amplitude and activation properties. Results： （ 1 ） Acute hypoxia induced a brief and slightly increase in Na ~ current of human cortical pyramidal neurons followed by a long-lasting inhibition in amplitude （P 〈 0.05）. I-V curve and the activation curve of Na＋ currents were shifted leftwards （in the negative direction）. （2） AMPA receptor antagonist NBQX blocked the hypoxic increase of Na＋ currents （P 〈 0.01 ）, and enhanced the posthypoxic inhibition of Na＋ currents （P 〈 0.01 ） ; GABAA receptor antagonist Bicuculline had no significant effect on the hypoxic alterations of Na ＋ currents （ P 〉 0.05 ）. Both NBQX and bicuculline did not affect the shifting of I-V curve and activation curve. （3） 50 μmol/L resveratrol blocked the hypoxic increase of Na＋ currents of human cortical neurons （P 〈 0.01 ）, and aggravated the posthypoxic inhibition of Na＋ currents （P 〈 0.05 ） ; 100 μmol/L resveratrol significantly delayed the responses of Na＋ currents to acute hypoxia and completely blocked the hypoxic increase of Na＋ currents and decreased the posthypoxic inhibition （ P 〈 0.05 ）. The I-V curve and the activation curve of Na＋ currents were shifted to right by either 50 μmol/L or 100 μmol/L, approximating normal level. Conclusion： Acute hypoxia mainly caused long-lasting inhibition in Na＋ currents of human cortical pyramidal neurons. AMPA receptor may affect the responses of Na＋ channel to acute hypoxia. The effects of resveratrol upon hypoxic responses of Na＋ currents of human cortical neurons may be concentration-dependent. Low concentratio

关 键 词：缺氧 Na+电流 人脑皮层锥体神经元 白藜芦醇 

分 类 号：R285[医药卫生—中药学]