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Naoxintong Protects Against Cerebral Ischemia-reperfusion Via Activating Akt, CREB and Bcl-2

Author: KangNing
Tutor: ZhangXiangJian
School: Hebei Medical University
Course: Neurology
Keywords: Cerebral ischemia Neuroprotection Naoxintong Apoptosis Akt
CLC: R743.31
Type: Master's thesis
Year: 2014
Downloads: 5
Quote: 0
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Objective: As Naoxintong (NXT) is proven to protect ischemia injury inheart and brain, through anti-inflammation, anti-oxidative stress and anti-apoptosis, this study was designed to assess the mechanism of neuroprotectiveeffects of Naoxintong against cerebral ischemia-reperfusion injury in micemiddle cerebral artery occlusion model.Methods: Adult male CD-1mice were randomly divided into five groups:Sham (sham-operated+0.9%saline), MCAO (MCAO+0.9%saline), Vehicle(MCAO+0.05%DMSO), NXT-L (MCAO+NXT360mg/kg), NXT-H(MCAO+NXT540mg/kg) and inhibitor (NXT540mg/kg+LY294002)groups. Mice were pre-administered NXT orally once daily for3days beforesurgery and then received once again30minutes before surgery. To confirmhow the neuroprotective effects of SIT might be affected if the PI3-K pathwaywas initially blocked, a PI3-K inhibitor, LY294002was intraventricularlyadministered to mice30min before reperfusion. Neurological deficit scores,infarct volume and brain water content were increased at24h after cerebralischemia-reperfusion. Additionally, the activities of Akt, CREB and Bcl-2inischemic brain cortex were evaluated by immunohistochemistry, western blot,RT-qPCR and immunofluorescent analysis at the same time.Results: Neurological deficit scores were increased in MCAO groupcompared with Sham control. Low dose of NXT reduced neurological deficitscores, but did not reach a significant level. NXT-H group exhibited asignificantly improved neurological function compared with MCAO group (P<0.05v.s. MCAO). No infarction was observed in sham-operated group.Corrected infarct volume (%HLV) was reduced from46.54%±4.24%inMCAO group to40.35%±6.96%in NXT-L group (NS v.s. MCAO) and to35.28%±5.92%in NXT-H group (P <0.05v.s. MCAO), suggesting that high dose of NXT significantly decreased infarct volume after MCAO.Assessmentof the effect of NXT on brain edema in contralateral and ipsilateralhemispheres showed that the water content of ipsilateral hemisphere wasreduced in NXT-H group compared with MCAO group (81.35%±1.75%vs.85.55%±0.93%, P <0.05).Quantitative analyses showed a significant increase of p-Akt, p-CREB,Bcl-2positive cells, western blot protein expression and mRNA expression inischemic cortex in NXT-H group compared with that in MCAO group (P <0.05vs. MCAO). However, low dose of NXT tended to increase p-Akt, p-CREB and Bcl-2expression though without statistically differences. Theelevated expression of p-Akt and p-CREB induced in NXT-H group wasattenuated by PI3-K inhibitor.Conclusions: We concluded that NXT protected the brain from ischemicinsult and it maybe through activating Akt, CREB and Bcl-2.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke) > Transient ischemic
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