异丙酚对大鼠海马脑片突触长时程增强效应的影响

目的观察异丙酚对大鼠海马脑片突触长时程增强（LTP）效应的影响及其机制,以探讨其影响记忆的机制。方法雄性SD大鼠断头,取出海马组织,制备400μm厚度的海马脑片。采用细胞外微电极记录大鼠海马脑片CA1区细胞外群体峰电位（PS）,然后施以100Hz的高频强直刺激（HFS）,诱发LTP产生,观察异丙酚（1～100μmol／L）对大鼠海马脑片LTP的影响及其与γ-氨基丁酸（GABA）受体的关系。结果与正常对照组比较,给予异丙酚1、5μmnol／L,HFS后其PS幅值无明显改变（均P＞0．05）;给予异丙酚10、30、50、100μmol／L,HFS后其PS幅值均明显降低,分别为124％±9％、112％±8％、106％±7％、102％±6％（均P＜0．01）。给予印防己毒素50μmol／L＋异丙酚50μmnol／L、荷包牡丹碱10μmol／L＋异丙酚50μmol／L,HFS后其平均PS幅值分别为150％±11％、147％±11％,与HFS前比较,其PS的增幅明显增加（均P＜0．01）,与正常对照组比较,其PS的幅值差异无统计学意义（均P＞0．05）,与异丙酚50μmol／L组比较,其PS增幅明显增加（均P＜0．01）。给予CGP353485μmol／L＋异丙酚50μmol／L,HFS后PS的幅值无明显改变（P＞0．05）,与正常对照组比较,其PS的幅值明显降低（P＜0．01）,与异丙酚50μmol／L组比较,其PS幅值差异无统计学意义（P＞0．05）。结论异丙酚能够抑制海马LTP的形成而影响记忆功能,其作用机制与活化大鼠海马GABAA受体有关,而与GABAB受体无关。

Effect of propofol on synaptic long-term potentiation in hippocampal slices of rats

OBJECTIVE: To investigate the effect of propofol on the synaptic long-term potentiation (LTP) in the CA(1) area of rats hippocampal slices and the possible mechanisms of its effect, and to elucidate the mechanisms underlying the effect of propofol on memory. METHODS: Hippocampal slices (400 microm thick) were obtained from male Sprague-Dawley rats (2 month old) that were ether-anesthetized and decapitated. The slices were prepared in artificial cerebrospinal fluid (ACSF), oxygenated with 95% O2 and 5% CO2. One glass electrode filled with superfusion solution was positioned in the pyramidal cell layer of the CA(1) area of rats hippocampal slices to simultaneously record evoked population spikes (PS). For LTP induction, high-frequency stimulation (HFS) conditioning pulses (100 Hz/1 s) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode. The present study was performed to determine the effect of propofol at concentrations of 1 - 100 micromol/L on the LTP induction in rats hippocampal slices and to explore the functional importance of gamma-aminobutyric acid (GABA) type receptors in the effect of propofol on LTP induction. RESULTS: The amplitude of the PS in hippocampal slices of rats was significantly increased by 52% +/- 12% after HFS compared with that of pre-HFS. The amplitude of the PS was not significantly changed after HFS by perfusion of propofol at concentrations of 1, 5 micromol/L, when compared with the value in control group. The amplitude of the PS after HFS in the presence of propofol at 10, 30, 50 and 100 micromol/L was 124% +/- 9%, 112% +/- 8%, 106% +/- 7%, 102% +/- 6% respectively, which was significantly decreased compared with the control (all P < 0.01). The amplitude of the PS under perfusion with 50 micromol/L propofol after HFS in the presence of 50 micromol/L picrotoxin or 10 micromol/L bicuculline was 150% +/- 11%, 147% +/- 11% respectively, which was dramatically increased compared with the value of pre-HSF and 50 micromol/L propofol (all P < 0.01), but did not differ significantly from the control group. The amplitude of the PS under perfusion with 50 micromol/L propofol after HFS in the presence of 5 micromol/L CGP35348 has no significant difference compared with the value of pre-HSF and 50 micromol/L propofol, but it was significantly lower than that in the control group (P < 0.01). CONCLUSION: The inhibition of LTP induction in hippocampus of rats may contribute to propofol-induced deficits in memory, and the underlying mechanism is involved in the activation of GABA(A) receptor other than GABA(B) receptor.