摘要
目的研究三羟异黄酮(GENISTEIN,GST)对静息状态下的海马脑片神经元活动的影响。方法应用细胞外记录单位放电技术。结果 (1)在48个CA1区神经元放电单位给予GST(10,50,100 ΜMOL/L)2 MIN,有46个放电单位(95.83%)放电频率明显降低,且呈剂量依赖性;(2)在9个CA1区神经元放电单位上,GST(50ΜMOL/ L)的抑制效应可被G蛋白激活的内向整流型钾通道(G PROTEIN-COUPLED INWARDLY RECTIFYING K+ CHANNELS,GIRK)阻断剂(TETRAETHYLAMMONIUM,TEA)1 MMOL/L完全阻断;(3)10个放电单位灌流一氧化氮合酶抑制剂(NG-NITRO-L-ARGININE METHYL ESTER,L-NAME)50ΜMOL/L,有9个单位(90.0%)放电明显增加,在此基础上灌流GST(50 ΜMOL/L)2 MIN,放电被抑制;(4)预先用0.2 MMOL/L的L-GLUTAMATE(L-GLU)灌流海马脑片,11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GST(50ΜMOL/L)2 MIN,其癫痫样放电被抑制。结论 GST可抑制海马神经元自发放电,并可抑制由L-NAME和L-GLUTAMATE诱发的神经元放电。提示GST对中枢神经元通过降低其活动而具有一定程度的保护作用,这种作用与钾电流有关,似与其激动GIRK促进K+外流引起细胞膜超极化以及NO 产生增加有关。
Objective To examine the effects of genistein ( GST ) on the discharges of neurons in CA1 area of hippocampal slices. Results ( 1 ) In response to the application of GST ( 10, 50, 100μmol/L; n = 48) into the perfusate for 2min, the spontaneous discharge rates (SDR) of 46/48 ( 95.83 % ) neurons were significantly decreased in a dosedependent manner. (2) In 9 neurons, the G protein-coupled inwardly rectifying K^+ (GIRK) channels antagonist, tetraethylammonium ( TEA 1mmol/L ) completely blocked the inhibitory effect of GST (50μmol/L). (3) Application of nitric oxide synthase ( NOS ) inhibitor NG-nitro-L-arginine methyl ester ( L-NAME, 50μmol/L ) into the perfusate for 2 min significantly augmented the SDR of 9/10( 90.0% ) neurons , then GST ( 50μmol/L ) applied into the perfusate reduced the increased SDR of all 9/9 ( 100% ) neurons. (4) Pretreatment with L-glutamate ( L-Glu, 0.2 mmol/L ) led to a marked increase in the SDR of all 11 ( 100% ) neurons in an epileptiform pattern. The increased discharges were also suppressed significantly after GST (50μmol/L) was applied into the perfusate for 2 min. Conclusion GST can inhibit the electrical activity of CA1 neurons. The inhibitory effect may be related to the activation of GIRK which induce K^+outward current and then engender the cell membrane hyperpolarization, and to the increased production of NO increase, which indicated that GST play a protective role on the central neurons.
出处
《神经科学通报》
CSCD
2005年第6期380-384,共5页
Neuroscience Bulletin