PI3K/Akt通路在丙泊酚减轻大鼠脑缺血性损伤中的作用

Propofol attenuates neuroinflammation and brain damage via modulating PI3K/Akt signaling pathway in rats of focal cerebral ischemia

目的研究PI3K/Akt信号通路在丙泊酚减轻大鼠缺血性脑损伤中的作用。方法制备大鼠脑缺血模型,随机分为对照组、溶媒组、丙泊酚治疗组和LY294002干预组,丙泊酚腹腔注射给药,LY294002脑室内给药。对大鼠神经功能损伤进行评分,测量大鼠脑梗死体积;分析大鼠缺血性脑水肿程度;检测脑组织髓过氧化物酶(MPO)的含量;Western blot法检测信号通路关键蛋白p-Akt、Akt的表达变化;ELISA法检测血浆TNF-α和IL-1β的分泌。结果丙泊酚能明显减轻大鼠神经功能障碍、脑梗死体积、脑水肿、MPO活性、TNF-α和IL-1β含量,丙泊酚的抗炎作用和神经保护作用被LY294002抑制。丙泊酚上调p-Akt的表达,这种作用也被LY294002抑制。结论 PI3K/Akt信号通路在丙泊酚减轻脑缺血诱导的脑损伤过程中起重要的调节作用。

Aim To explore whether propofol attenuates neuroinflammation and brain damage via modulating PI3K/Akt signaling pathway following focal cerebral ischemia in rats,and further investigate the possible mechanisms. Methods Sprague-Dawley rats which underwent the cerebral ischemic injury by the suture occlusion model were randomly divided into sham operation,MCAO,propofol-treated and LY294002 groups.Neurological deficit scores,cerebral infarct size,and cerebral water content were measured,then the myeloperoxidase (MPO) activities in rat brain were measured as an index of neutrophil infiltration.The content of TNF-α and IL-1β in blood was determined using ELISA;the expressions of p-Akt and Akt in rat brain were detected by Western blot. Results Propofol reduced neurological deficit scores,cerebral infarct size,cerebral water content,MPO activity,TNF-α and IL-1β content,which were all abolished by LY294002.Propofol up-regulated the expression of p-Akt,which was inhibited by LY294002. Conclusion Propofol attenuates neuroinflammation and ischemic brain damage via modulating the PI3K/Akt signaling pathway.