[丙泊酚对大鼠海马脑片突触长时程增强的影响]

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

作者信息

Feng Chun-Sheng, Qiu Jin-Peng, Ma Hai-Chun, Yue Yun

机构信息

Department of Anesthesiology, First Hospital of Jilin University, Changchun 130021, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Mar 20;87(11):763-7.

PMID:17565847

Abstract

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.

摘要

目的

研究丙泊酚对大鼠海马脑片CA1区突触长时程增强（LTP）的影响及其作用机制，以阐明丙泊酚影响记忆的机制。

方法

取2月龄雄性Sprague-Dawley大鼠，乙醚麻醉后断头，获取厚度为400μm的海马脑片。脑片置于人工脑脊液（ACSF）中，用95% O₂和5% CO₂ 进行氧合。将一根充满灌流液的玻璃电极置于大鼠海马脑片CA1区的锥体细胞层，同步记录诱发群体峰电位（PS）。为诱导LTP，使用双极刺激电极对海马的Schaffer侧支-连合通路施加高频刺激（HFS）条件脉冲（100Hz/1s）。本研究旨在确定1 - 100μmol/L浓度的丙泊酚对大鼠海马脑片LTP诱导的影响，并探讨γ-氨基丁酸（GABA）型受体在丙泊酚对LTP诱导作用中的功能重要性。

结果

与高频刺激前相比，高频刺激后大鼠海马脑片PS的幅度显著增加了52%±12%。与对照组相比，灌注1、5μmol/L丙泊酚后高频刺激时PS的幅度无明显变化。在10、30、50和100μmol/L丙泊酚存在下高频刺激后PS的幅度分别为124%±9%、112%±8%、106%±7%、102%±6%，与对照组相比均显著降低（均P<0.01）。在50μmol/L苦味毒或10μmol/L荷包牡丹碱存在下，50μmol/L丙泊酚灌注后高频刺激时PS的幅度分别为150%±11%、147%±11%，与高频刺激前及50μmol/L丙泊酚组相比均显著增加（均P<0.01），但与对照组无显著差异。在5μmol/L CGP35348存在下，50μmol/L丙泊酚灌注后高频刺激时PS的幅度与高频刺激前及50μmol/L丙泊酚组相比无显著差异，但显著低于对照组（P<0.01）。