白藜芦醇抑制大鼠下丘脑脑片室旁核神经元放电(英文)

Resveratrol inhibits electrical activity of paraventricular nucleus neurons in rat hypothalamic slices

本文旨在研究白藜芦醇(resveratrol)对下丘脑脑片室旁核神经元放电的影响。应用玻璃微电极细胞外记录单位放电技术,在下丘脑脑片上观察白藜芦醇对静息状态下室旁核神经元放电的影响。结果如下:(1)在29张下丘脑脑片室旁核神经元放电单位给予白藜芦醇(0.05,0.5,5.0μmol/L)2min,有28张脑片(96.6%)放电频率显著降低,且呈剂量依赖性;(2)预先用0.2mmol/L的L-glutamate灌流8张下丘脑脑片,8张脑片(100%)放电频率显著增加,表现为癫痫样放电,该放电可被白藜芦醇(5.0μmol/L)灌流2min抑制;(3)预先用L型钙通道开放剂Bay K8644(0.1μmol/L)灌流8张下丘脑脑片,8张脑片(100%)放电频率显著增加,该放电可被白藜芦醇(5.0μmol/L)灌流2min抑制;(4)用一氧化氮合酶抑制剂Nω-nitro-L-arginine methyl ester(L-NAME)50μmol/L灌流8张下丘脑脑片,7张脑片(87.5%)放电频率显著增加,该放电可被白藜芦醇(5.0μmol/L)灌流2min抑制。以上结果提示,白藜芦醇抑制下丘脑室旁核神经元自发放电,可能通过降低心血管中枢的活动性而产生中枢保护作用。这种抑制作用可能与白藜芦醇抑制L型钙通道、减少钙内流有关,与NO释放无关。

To study the role of resveratrol in the discharges of neurons in paraventricular nucleus （PVN） in hypothalamic slices, extracellular single-unit discharge recording technique was used. The effects of resveratrol were examined with glass microelectrodes in the rat PVN neurons at resting potential level. The results were as follows： （1） In response to the application of resveratrol （0.05, 0.5, 5.0 μmol/L, n=29） to the superfusate for 2 rain, the spontaneous discharge rate （SDR） of neurons in 28/29 （96.6%） hypothalamic slices significantly decreased in a dose-dependent manner; （2） Pretreatment with L-glutamate （0.2 retool/L） led to a marked increase in the SDR in all 8/8 （100%） slices in an epileptiform pattern. The increased discharges were suppressed by the application of resveratrol （5.0 μmol/L） in all 8 slices; （3） In 8 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 （0.1 μmol/L）, induced a significant increase in the discharge rate in 8/8 （100%） slices. Resveratrol （5.0 μmol/L） significantly attenuated the increased SDR in all 8 slices; （4） Pretreatment with the nitric oxide synthase （NOS） inhibitor N^ω-nitro- L-arginine methyl ester （L-NAME, 50 μmol/L） increased SDR in 7/8 （87.5%） slices, but did not affect the inhibitory effect of resveratrol （5.0 μmol/L）. These results suggest that resveratrol inhibits the electrical activity of PVN neurons and exerts neuroprotective actions on central neurons. The inhibitory effect of resveratrol is possibly related to the blockade of L-type calcium channel, but not due to NO release.