Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P.R. China.
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, PR China.
Sci Rep. 2017 Jun 8;7(1):3039. doi: 10.1038/s41598-017-03404-6.
Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion. In vitro, primary cultured neurons were treated by calycosin, then exposed to 2 h oxygen glucose deprivation (OGD) followed by 24 h reoxygenation. Our results showed that treatment with calycosin protected against ischemia-induced damages by increasing TRPC6 and P-CREB expression and inhibiting calpain activation. The neuroprotection effect of calycosin was diminished by inhibition or knockdown of TRPC6 and CREB. These findings indicated that the potential neuroprotection mechanism of calycosin was involved with TRPC6-CREB pathway.
我们之前的研究已经提供了证据表明毛蕊异黄酮可以保护大脑免受缺血/再灌注损伤，但它的机制尚不完全清楚。瞬时受体电位经典型 6（TRPC6）在促进神经元对脑缺血损伤的存活中起着关键作用。本研究旨在通过 TRPC6-CREB 通路来检验毛蕊异黄酮是否对脑缺血损伤具有保护作用。在体内，大鼠短暂性大脑中动脉闭塞（MCAO） 2 小时，然后在再灌注开始时给予不同剂量的毛蕊异黄酮治疗。在体外，原代培养神经元用毛蕊异黄酮处理，然后暴露于 2 小时氧葡萄糖剥夺（OGD），再进行 24 小时复氧。我们的结果表明，毛蕊异黄酮通过增加 TRPC6 和 P-CREB 的表达并抑制钙蛋白酶的激活来对抗缺血引起的损伤。TRPC6 和 CREB 的抑制或敲低减弱了毛蕊异黄酮的神经保护作用。这些发现表明，毛蕊异黄酮的潜在神经保护机制涉及 TRPC6-CREB 通路。
