三羟异黄酮对大鼠海马CA1区神经元自发放电的影响(英文)

Effects of genistein on neuronal discharges in rat hippocampal CA1 area

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.