Neuroprotective effect of calcitriol on ischemic/reperfusion injury through the NR3A/CREB pathways in the rat hippocampus
Neuroprotective effect of calcitriol on ischemic/reperfusion injury through the NR3A/CREB pathways in the rat hippocampus
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DOI：
10.3892/mmr.2013.1734
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发表时间：
2013-12-01
影响因子：
3.4
通讯作者：
Ran, Ran
中科院分区：
文献类型：
--
作者：
Fu, Jun;Xue, Rui;Ran, Ran
骨化三醇已被证明对缺血/再灌注(I/R)损伤具有神经保护作用。然而，这种保护的确切机制仍不清楚。本研究观察了骨化三醇对大鼠大脑中动脉闭塞(MCAO)所致脑I/R损伤的神经保护作用。此外，在海马神经元中，NR3A、细胞外信号调节激酶1/2(ERK1/2)和磷酸化cAMP/钙反应元件结合蛋白(p-CREB)参与了这一保护作用。Western印迹分析NR3A、丝裂原活化蛋白激酶(MEK)和p-CREB的蛋白表达水平。用量子点免疫荧光分析法检测p-CREB和NR3A的免疫反应性。结果显示，MCAO大鼠大脑皮质梗死体积较大。相比之下，腹腔注射骨化三醇显著减少再灌流后7天的脑梗塞体积，这些结果伴随着海马神经元NR3A和p-CREB活性的升高。加入PD98059抑制MEK后，骨化三醇的神经保护作用减弱，CREB活性相应降低。骨化三醇通过NR3A-MEK/ERK-CREB通路对脑I/R损伤具有保护作用。
Calcitriol has been demonstrated to provide neuroprotection against ischemia/reperfusion (I/R) injury. However, the exact mechanism of this protection remains unknown. In the present study, the neuroprotective effect of calcitriol was investigated in rats exposed to cerebral I/R injury induced by middle cerebral artery occlusion (MCAO). In addition, the involvement of NR3A, extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated cAMP/Ca2+-response element binding protein (p-CREB) in this protective action was determined in the hippocampal neurons. Western blot analysis was conducted to analyze the protein levels of NR3A, mitogen-activated protein kinase kinase (MEK) and p-CREB. The immunoreactivity of p-CREB and NR3A were measured by quantum dot-based immunofluorescence analysis. Results showed that MCAO rats exhibited large cortical infarct volumes. By contrast, intraperitoneal administration of calcitriol significantly reduced infarct volumes seven days following reperfusion, and these results were accompanied by elevated NR3A and p-CREB activity in the hippocampal neurons. The inhibition of MEK by the addition of PD98059 led to attenuation of the neuroprotective effects of calcitriol and a correlated decrease in CREB activity. The results also demonstrated that calcitriol protected the brain from I/R injury through the NR3A-MEK/ERK-CREB pathway.