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白藜芦醇抑制大鼠海马 CA1区神经元放电

李明, 王庆山, 陈怡, 王泽民, 刘政, 郭淑梅

河北医科大学基础医学研究所生理室. 河北, 石家庄 050017；河北医科大学病理学教研室. 河北, 石家庄 050017

摘要

应用细胞外记录单位放电技术,在大鼠海马脑片上观察了白藜芦醇(resveratrol)对海马CA1区神经元放电的影响.实验结果如下:在52个CA1区神经元放电单位给予白藜芦醇(0.05、0.5、5 μmol/L)2 min,有46个放电单位(88.5%)放电频率明显降低,且呈剂量依赖性;预先用0.2 mmol/L的L-glutamate灌流海马脑片,8个放电单位放电频率明显增加,表现为癫痫样放电,在此基础上灌流白藜芦醇(5 μmol/L)2 min,其癫痫样放电被抑制;预先用L型钙通道开放剂Bay K8644灌流7个海马脑片,有6个单位(85.7%)放电增加,在此基础上灌流白藜芦醇(5 μmol/L)2 min,其放电被抑制;9个放电单位灌流一氧化氮合酶抑制剂L-NAME(NG-nitro-L-arginine methyl ester)50 μmol/L,有7个单位(77.8%)放电明显增加,在此基础上灌流白藜芦醇(5 μmol/L)2 min,放电被抑制;10个放电单位灌流大电导钙激活性钾通道阻断剂TEA(tetraethylammonium chloride)1 mmol/L后,有9个单位(90%)放电增加,在此基础上灌流白藜芦醇(5 μmol/L)2min,8个放电单位(88.9%)放电频率明显减低.以上结果提示:白藜芦醇能抑制海马神经元自发放电以及由L-glutamate、L-NAME、Bay K8644和TEA诱发的放电,可能与白藜芦醇抑制L型钙通道,减少钙内流有关;似乎与大电导钙激活性钾通道无关。

关键词： 海马; 白藜芦醇; 钙通道

Resveratrol inhibits neuronal discharges in rat hippocampal CA1 area

Li Ming, Wang Qingshan, Chen Yi, Wang Zemin, Liu Zheng, Guo Shumei

Laboratory of Physiology

Abstract

The effects of resveratrol on the discharges of neurons in CA1 area of rat hippocampal slices were examined by using extracellular recording technique. The results are as follows: In response to the application of resveratrol (0.05, 0.5, 5.0 #mu#mol/L,n=52) into the superfusate for 2 min, the spontaneous discharge rate of 46/52 (88.5%) neurons was significantly decreased in a dosedependent manner; Application of L-glutamate (0.2 mmol/L) into the superfusate led to a marked increase in discharge rate of all 8 (100%) slices in an epileptiform pattern. The increased discharges weresuppressed by application of resveratrol (5.0 #mu#mol/L); In 7 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 (0.1 #mu#mol/L), induced a significant increase in the discharge rate of 6/7 (85.7%) slices. The increased discharges were suppressed by application of resveratrol (5.0 #mu#mol/L); In 9 slices,perfusion of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 #mu#mol/L) into the superfusate significantly augmented the discharge rate of 7/9 (77.8%) slices. Resveratrol (5.0 #mu#mol/L) applied into the superfusate reduced the increased discharges of all 7/7 (100%) neurons; In 10 units, the large-conductance Ca~(2+)-activated K~(+) channel blocker (tetraethylammonium chloride, TEA, 1 mmol/L) significantly increased the discharge rate of 9/10 (90%) slices. Resveratrol (5.0 #mu#mol/L) applied into the superfusate inhibited the discharges of 8/9 (88.9%) slices. These results suggest that resveratrol inhibits the electrical activity of CA1 neurons. This effect may be related to the blockade of L-type calcium channel and a subsequent reduction of calcium influx, and probably has no association with large-conductance Ca~(2+)-activated K~(+) channel.

Key words: Hippocampus;resveratrol;Calcium channel

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引用本文：

李明, 王庆山, 陈怡, 王泽民, 刘政, 郭淑梅. 白藜芦醇抑制大鼠海马 CA1区神经元放电[J]. 生理学报 2005; 57 (3): .

Li Ming, Wang Qingshan, Chen Yi, Wang Zemin, Liu Zheng, Guo Shumei. Resveratrol inhibits neuronal discharges in rat hippocampal CA1 area. Acta Physiol Sin 2005; 57 (3): (in Chinese with English abstract).