Yuan Zhao1, Baosheng Fu2, Xiangjian Zhang3, Ting Zhao1, Linyu Chen4, Jian Zhang4, Xiaolu Wang5. 1. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China. 2. Department of Gereology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China. 3. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China; Hebei Collaborative Innovation Center for Cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China. Electronic address: zhang6xj@aliyun.com. 4. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China; Hebei Collaborative Innovation Center for Cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China. 5. Hebei Collaborative Innovation Center for Cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China. Electronic address: wangxl2014@yahoo.com.
Abstract
BACKGROUND: Oxidative damage plays a pivotal role in the pathogenesis of cerebral ischemic stroke and may represent a target for treatment. Our previous studies have proved that nuclear factor E2-related factor 2 (Nrf2) and its downstream genes served as a key mechanism for protection against oxidative stress. Paeonol (PN) is reputed to possess a broad range of therapeutic properties probably by virtue of its antioxidative ability. However little is elucidated regarding the underlying mechanisms in ischemic stroke. The aim of this study was to explore PNs effect in ischemic injury and the role of the pAkt, Nrf2 and hemeoxygenase-1 (HO-1) in the mice brains of permanent middle cerebral artery occlusion (pMCAO). METHODS: Male CD-1 mice were subjected to pMCAO and randomly divided into five groups: Sham (sham-operated+0.9% saline), pMCAO (pMCAO+0.9% saline), Vehicle (pMCAO+vehicle), PN-L (pMCAO+PN 30 mg/kg) and PN-H (pMCAO+PN 60 mg/kg) groups. PN was pre-administered intragastrically once daily for 3 days and with the last administration at 30 min before the operation in the fourth day. Neurological deficit scores, brain water content and infarct volume were measured at 24h after pMCAO. Western blot and qRT-PCR were employed to determine the expressions of pAkt, Nrf2, HO-1 and claudin-5. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by spectrophotometer. RESULTS: Compared with Vehicle group, PN significantly alleviated neurological deficit, infarct volume and brain edema (P<0.05), upregulated the expression of pAkt, Nrf2, HO-1 and SOD (P<0.05), decreased the level of MDA (P<0.05). Meanwhile, the expression of claudin-5 was also enhanced. CONCLUSIONS: PN reduced ischemic brain injury after pMCAO; this effect may be accompanied with upregulation of pAkt, Nrf2, HO-1 and ameliorating BBB permeability.
BACKGROUND: Oxidative damage plays a pivotal role in the pathogenesis of cerebral ischemic stroke and may represent a target for treatment. Our previous studies have proved that nuclear factor E2-related factor 2 (Nrf2) and its downstream genes served as a key mechanism for protection against oxidative stress. Paeonol (PN) is reputed to possess a broad range of therapeutic properties probably by virtue of its antioxidative ability. However little is elucidated regarding the underlying mechanisms in ischemic stroke. The aim of this study was to explore PNs effect in ischemic injury and the role of the pAkt, Nrf2 and hemeoxygenase-1 (HO-1) in the mice brains of permanent middle cerebral artery occlusion (pMCAO). METHODS: Male CD-1 mice were subjected to pMCAO and randomly divided into five groups: Sham (sham-operated+0.9% saline), pMCAO (pMCAO+0.9% saline), Vehicle (pMCAO+vehicle), PN-L (pMCAO+PN 30 mg/kg) and PN-H (pMCAO+PN 60 mg/kg) groups. PN was pre-administered intragastrically once daily for 3 days and with the last administration at 30 min before the operation in the fourth day. Neurological deficit scores, brain water content and infarct volume were measured at 24h after pMCAO. Western blot and qRT-PCR were employed to determine the expressions of pAkt, Nrf2, HO-1 and claudin-5. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by spectrophotometer. RESULTS: Compared with Vehicle group, PN significantly alleviated neurological deficit, infarct volume and brain edema (P<0.05), upregulated the expression of pAkt, Nrf2, HO-1 and SOD (P<0.05), decreased the level of MDA (P<0.05). Meanwhile, the expression of claudin-5 was also enhanced. CONCLUSIONS:PN reduced ischemic brain injury after pMCAO; this effect may be accompanied with upregulation of pAkt, Nrf2, HO-1 and ameliorating BBB permeability.