中文摘要：

β-淀粉样蛋白（β-amyloid protein,Aβ）对突触可塑性和认知功能的伤害效应已被广泛报道,但机制尚不明确。本研究通过观察Aβ25-35和蛋白酪氨酸激酶（protein tyrosine kinase,PTK）特异性抑制剂genistein对大鼠在体海马CA1区长时程增强（long-term potentiation,LTP）的效应,揭示Aβ抑制海马LTP可能的PTK机制。实验采用电生理学方法,利用自制的刺激/记录绑定电极引导和记录大鼠在体海马CA1区场兴奋性突触后电位（field excitatory postsynaptic potentials,fEPSPs）、双脉冲易化（paired-pulse facilitation,PPF）以及高频刺激（high-frequency stimuli,HFS）诱导的LTP。结果显示：（1）侧脑室内注射Aβ25-35（20nmol）不影响基础性fEPSPs,但能显著抑制HFS诱导的LTP,fEPSPs平均幅度较对照组明显降低;（2）类似于Aβ25-35的效应,侧脑室内注射genistein（200nmol）也不影响基础性fEPSPs,但明显抑制HFS诱导的LTP,具有与Aβ25-35有相似的压抑程度;（3）联合给予Aβ25-35（20nmol）和genistein（200nmol）后,两者对LTP产生的抑制效应并未进一步加强,与单独给予Aβ25-35或genistein的压抑效应相比,没有显著区别;（4）分别或联合给予Aβ25-35和genistein均未影响海马CA1区PPF。以上结果表明,脑室内注射Aβ25-35能够明显抑制大鼠在体海马CA1区HFS诱发的LTP,提示阿尔茨海默病时脑内产生的Aβ有可能通过影响海马突触可塑性而伤害学习和记忆功能;Aβ25-35和PTK抑制剂genistein对海马LTP表现出的同等程度抑制以及联合给药后效应维持不变,提示PTK系统可能参与了Aβ对在体大鼠海马LTP的抑制。

英文摘要：

Although the impairing effects of β-amyloid （Aβ） protein on synaptic plasticity and cognitive function have been widely reported, the mechanisms underlying the neurotoxicity of Aβ are still not well known. The present study observed the effects of intracerebroventricular （i.c.v.） injection of both Aβ25-35 and genistein （a specific tyrosine kinase inhibitor at high concentration） on the hippocampal long-term potentiation （LTP） in the CA1 region, and investigated its possible protein tyrosine kinase （PTK） mechanism. Male Wistar rats were surgically prepared for acute LTP recordings in vivo. Two parallel bond electrodes for stimulating and recording were simultaneously inserted into the right hippocampus of rats. The field excitatory postsynaptic potentials （fEPSPs）, paired-pulse facilitation （PPF） and high-frequency stimuli （HFS）-induced LTP were recorded by delivering test stimuli, paired pulses and HFS to the Schaffer-collateral/commissural pathway. The results showed that： （1） i.c.v, injection of Aβ25-35 did not affect the baseline synaptic transmission, but significantly suppressed the HFS-induced LTP, with a decreased average amplitude of fEPSPs [（129.2±6.7）% in 10 nmol A~25_35 group; （110.6±8.6）% in 20 nmol Aβ25-35 group P〈0.01] at 1 h post-HFS when compared to that in the control group [（163.1±8.1）%]; （2） Similarly, i.c.v, injection of genistein （200 nmol） did not change the basic synaptic transmission, but significantly suppressed HFS-induced LTP, with the similar average amplitude of fEPSPs [（114.0±7.2）%] at 1 h post-HFS to that in 20 nmol A1125-35 group; （3） Co-application of Aβ25-35 （20 nmol） and genistein （200 nmol） caused no additive suppression of LTP, and the average amplitude of fEPSPs was （113.0±8.8）% at 1 h post-HFS, showing no significant difference when compared with that in Aβ25-35 or genistein alone groups （P〉0.05）; （4） There was no significant change in the PPF following genistein and Aβ25-