Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Clin Exp Med. 2012 Mar;12(1):31-7. doi: 10.1007/s10238-011-0139-4. Epub 2011 May 24.
Upon CNS injury, adenosine-5'-triphosphate is released and acts on P2X7 receptors, which might influence many cytokines secretion from glial cells and, in turn, affects the survival of neurons. Propofol, an intravenous anesthetic, has been shown to provide neuroprotective effect. However, the effect of propofol on astrocyte-associated processes remains to be clarified. In this study, we investigated the effects of propofol on P2X7 activity in astrocytes and tumor necrosis factor-α (TNF-α) secretion from these cells and thereby to infer the possible role(s) of glial P2X7 receptors in propofol neural protective effects. Whole-cell patch clamp results showed that in clinically relevant concentrations (3.3, 10 or 33 μM), propofol increased the P2X7 current amplitudes significantly and propofol in 10 μM extended the inactivation times of P2X7 receptors. Enzyme-linked immunosorbent assay showed that propofol increased the secretion of TNF-α from astrocytes in high concentration (300 μM), while inhibited in clinically relevant concentration (10 μM). Both of these effects were not influenced by Brilliant blue G. These results suggest that in clinically relevant concentrations, propofol increases the activity of P2X7 receptors in activated astrocytes, but this does not contribute to the downregulation of the secretion of TNF-α.
中枢神经系统损伤后，三磷酸腺苷（adenosine-5'-triphosphate）被释放并作用于 P2X7 受体，这可能影响胶质细胞中许多细胞因子的分泌，进而影响神经元的存活。丙泊酚是一种静脉麻醉剂，已被证明具有神经保护作用。然而，丙泊酚对星形胶质细胞相关过程的影响仍有待阐明。在这项研究中，我们研究了丙泊酚对星形胶质细胞中 P2X7 活性和这些细胞中肿瘤坏死因子-α（TNF-α）分泌的影响，从而推断出神经保护作用中可能涉及的胶质细胞 P2X7 受体的作用。全细胞膜片钳结果表明，在临床相关浓度（3.3、10 或 33μM）下，丙泊酚显著增加 P2X7 电流幅度，丙泊酚在 10μM 时延长 P2X7 受体的失活时间。酶联免疫吸附试验表明，丙泊酚在高浓度（300μM）下增加星形胶质细胞中 TNF-α的分泌，而在临床相关浓度（10μM）下抑制其分泌。这两种作用均不受亮蓝 G 的影响。这些结果表明，在临床相关浓度下，丙泊酚增加了激活星形胶质细胞中 P2X7 受体的活性，但这并不有助于下调 TNF-α的分泌。
