The Role of TRPC6 in the Neuroprotection of Calycosin Against Cerebral Ischemic Injury

被引:54
作者
Guo, Chao [1 ]
Ma, Yongyuan [2 ]
Ma, Shanbo [1 ]
Mu, Fei [1 ]
Deng, Jiao [2 ]
Duan, Jialin [1 ]
Xiong, Lize [2 ]
Yin, Ying [1 ]
Wang, Yanhua [1 ]
Xi, Miaomaio [1 ]
Wen, Aidong [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian 710032, Peoples R China
基金
中国国家自然科学基金;
关键词
REPERFUSION INJURY; ARTERY-OCCLUSION; CALPAIN SYSTEM; BRAIN-DAMAGE; RAT MODEL; CHANNELS; ACTIVATION; INHIBITION; STROKE; ACID;
D O I
10.1038/s41598-017-03404-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:13
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