Inhibition of microglial activation contributes to propofol-induced protection against post-cardiac arrest brain injury in rats
Inhibition of microglial activation contributes to propofol-induced protection against post-cardiac arrest brain injury in rats
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抑制小胶质细胞活化有助于丙泊酚诱导的大鼠心脏骤停后脑损伤的保护
DOI：
10.1111/jnc.13179
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wang W;Lu R;Feng DY;Liang LR;Liu B;Zhang H
有研究表明，异丙酚可以调节小胶质细胞的活性，因此可能对脑缺血损伤后的神经炎症具有潜在的作用。然而，丙泊酚是否以及如何通过抑制小胶质细胞活化来抑制心脏骤停后脑损伤仍不清楚。建立窒息心脏骤停（CA）大鼠模型，然后进行心肺复苏。CA诱导海马CA 1区显著的小胶质细胞活化，表现为OX 42和P2类嘌呤受体7（P2 X7 R）表达增加以及p38 MAPK磷酸化。Morris水迷宫显示，用小胶质细胞抑制剂米诺环素或丙泊酚预处理可以抑制或减轻CA后的学习和记忆障碍。丙泊酚可能通过P2 X7 R/p-p38通路显著抑制小胶质细胞活化。体外实验表明，异丙酚预处理可抑制ATP诱导的小胶质细胞活化及肿瘤坏死因子-α和白细胞介素-1 β的释放。此外，当与ATP处理的小胶质细胞共培养时，丙泊酚保护神经元免受损伤。我们的数据表明，丙泊酚预处理抑制CA诱导的海马小胶质细胞活化和神经元损伤，并最终改善认知功能。我们提出了丙泊酚介导的心脏骤停（CA）后脑保护的可能机制。CA诱导小胶质细胞中的P2 X7 R上调和p38磷酸化，这诱导TNF-α和IL-1β的释放以及随后的神经元损伤。异丙酚可抑制小胶质细胞活化，减轻神经元损伤。我们的研究结果表明，丙泊酚诱导的抗炎治疗是CA后脑损伤治疗干预的合理策略。
It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post‐cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre‐treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p‐p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol.In vitroexperiment showed that propofol pre‐treatment inhibited ATP‐induced microglial activation and release of tumor necrosis factor‐α and interleukin‐1β. In addition, propofol protected neurons from injury when co‐culturing with ATP‐treated microglia. Our data suggest that propofol pre‐treatment inhibits CA‐induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function.We proposed a possible mechanism of propofol‐mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF‐α and IL‐1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol‐induced anti‐inflammatory treatment as a plausible strategy for therapeutic intervention in post‐CA brain injury.