Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice
Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice
复制标题
抑制神经元特异性 CREB 去磷酸化参与丙泊酚和氯胺酮诱导的小鼠脑缺血性损伤的神经保护作用
DOI：
10.1007/s11064-011-0582-3
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Li, Junfa
中科院分区：
文献类型：
--
作者：
Shu, Luowa;Li, Tianzuo;Li, Junfa
异丙酚和氯胺酮可提供一定程度的神经保护，但其机制尚不清楚。cAMP反应元件结合蛋白（CREB）的丝氨酸133位磷酸化（P-CREB）被认为是参与神经保护的一个汇聚点。本研究的目的是确定不同剂量的异丙酚和氯胺酮是否可以提供对永久性大脑中动脉闭塞（MCAO）诱导的缺血性损伤和P-CREB的参与的神经保护。将80只成年雄性BALB/c小鼠随机分为假手术组、MCAO +生理盐水组、MCAO +丙泊酚25、50、100 mg/kg组和MCAO +氯胺酮25、50、100 mg/kg组（MCAO后30 min腹腔注射）。结果发现，与MCAO +生理盐水组（n = 6）相比，异丙酚50、100（而非25）mg/kg和氯胺酮25（而非50和100）mg/kg可显著缩小脑梗死体积、水肿率和神经功能缺损（n = 10/组），并抑制梗死周围区P-CREB水平的降低。此外，双标记免疫荧光染色结果显示，P-CREB与神经元特异性标记物NeuN共定位于50 mg/kg丙泊酚和25 mg/kg氯胺酮处理6 h MCAO小鼠的梗死周围区域（n = 4/组）。这些结果表明，抑制梗死周围神经元特异性P-CREB去磷酸化参与了高剂量异丙酚和低剂量氯胺酮诱导的6 h MCAO小鼠的神经保护作用。
Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.