摘要
目的研究染料木黄酮(GST)在心血管中枢神经系统的作用。方法应用细胞外记录单位放电技术,在下丘脑脑片上观察GST对静息状态下的室旁核神经元放电的影响。结果①26个脑片分别灌流GST 10,50,100μmol·L^(-1)2 min,有25个脑片放电频率明显降低,且呈浓度依赖性;②用0.2 mmol·L^(-1) L-谷氨酸灌流脑片,7/7个脑片放电频率明显增加,表现为癫痫样放电,在此基础上加灌GST 50μmol·L^(-1)2 min,其癫痫样放电被抑制;③用G蛋白激活的内向整流型钾通道阻断剂四乙胺1 mmol·L^(-1)灌流脑片,约10 min后加入GST 50μmol·L^(-1),8/8个脑片的放电抑制效应被完全阻断;④用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯50μmol·L^(-1)灌流脑片,7/7个脑片的放电频率增加,在此基础上加灌GST 50μmol·L^(-1)2 min,放电被抑制。结论GST可抑制下丘脑室旁核神经元自发放电,并抑制L-谷氨酸诱发的神经元癫痫样放电。这种抑制作用可能与激活G蛋白激活的内向整流型钾通道,促进K^+外流,从而引起细胞膜超极化有关;而与NO释放无关。GST可能通过降低心血管中枢的活动性而产生一定的心血管系统保护作用。
AIM To study the central role of genistein (GST) in regulating cardiovascular function of nervous center by examining the effects of GST on the electrical activity of rat paraventricular nucleus neurons in slice preparation and to elucidate the mechanism involved. METHODS Using extracellular single-unit discharge recording technique to examine discharges of neurons in paraventricular nucleus of hypothalamic slices at the resting potential level. RESULTS (1)In response to the application of GST 10, 50 and 100 μmol.L^-1 , respectively, in the perfusate for 2 min, the spontaneous discharge rates (SDR) of neurons in 25/26 hypothalamic slices were significantly decreased in a concen- tration-dependent manner. (2)Pretreatment with L-glutamate 0.2 mmol · L^-1 led to a marked increase in the SDR of slices in an epileptiform pattern. GST 50 μmol. L^-1 significantly attenuated the increased SDR in all 7 slices. (3)In 8/8 slices, the G protein-coupled inward- ly rectifying K ^* channels (GIRKs) antagonist, tetraethylammonium 1 mmol. L^-1 completely blocked the inhibitory effect of GST 50 μmol. L^-1. (4)Pretreatment with nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester 50 μmol· L^-1 increased SDR in all 7 slices, but did not affect the inhibitory effect of GST 50 μmol·L^-1. CONCLUSION GST can inhibit the electrical activity of paraventricular neurons, and play a protective role on the central neurons. The inhibitory effect of GST may be related to the activation of GIRKs which induce K ^+ outward current and then engender the cell membrane hyperpolarization, but be not due to the NO release.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2007年第4期241-246,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(304005)
河北省自然科学基金(303467)~~
关键词
室旁核
神经元
染料木黄酮
微电极
paraventricular nucleus
neurons
genistein
microelectrodes