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| Effects of [Gly14]-Humanin on oxidative stress and neuron apoptosis in rats after focal cerebral ischemia reperfusion injury |
| YU Zhi*, YU Min, GU Su-bing, SHAO Xiao-li, HONG Xiao-qin, ZHANG Teng
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| *Department of Neurology,The First People's Hospital of Chun'an,Hangzhou,Zhejiang 311700,China |
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Abstract Objective To study the effect of [Gly14]-Humanin on oxidative stress and neuron apoptosis after focal cerebral ischemia reperfusion injury in rats. Methods A rat model of acute middle cerebral artery occlusion（MCAO）and reperfusion was established by suture embolism. Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham-operation group,model group,normal saline group and HNG group. And 5 μL HNG（100 nmol/L） in the rats of the HNG group,normal saline in the rats of the sham-operation group and normal saline group were given to rats 3 days before operation respectively（iv,three times,qd）. After cerebral ischemia 3 h and 24 h of reperfusion,neurological deficit score（NDS）were performed for each group,and the activity of sod,levels of GSH and MDA in cerebral tissue were detected. TUNEL staining were used to detect neuronal apoptosis. Results Median（Interquartile range）of NDS was 0（0）in sham-operation group,1.5（1）in model group,3（1）in normal saline group and 3（1）in HNG group,respectively,and the NDS of sham-operation group was significantly lower than the other three groups. The NDS of HNG group was significantly lower than the model group and normal saline group（all P<0.05）. Compared with sham-operation group,the activity of SOD of model group,normal saline group and HNG group rats[（11.65±1.66）,（12.15±1.56） and （19.43±1.47）U/mL] and levels of GSH [（8.84±1.23）,（7.51±1.16） and （11.17±1.67）mg/L]were decreased,and levels of MDA[（42.61±1.79）,（40.33±1.24）and （35.39±1.29）nmol/mL]were increased（P<0.05）. The activity of SOD and levels of GSH of HNG group were significantly higher than model group and normal saline group,but the levels of MDA was significantly lower than model group and normal saline group（all P<0.05）. Compared with sham-operation group[（0.13±0.01）%],percentage of neuronal apoptosis of model group,normal saline group and HNG group rats[（0.59±0.07）%,（0.51±0.08）% and （0.22±0.03）%,respectively]were increased（P<0.05）,and percentage of neuronal apoptosis of HNG group was significantly lower than model group and normal saline group（all P<0.05）. Conclusion By increasing the activity of SOD and levels of GSH,[Gly14]-Humanin can resist focal cerebral ischemia reperfusion injury,and can decrease the neuro apoptosis of ischemic area,thus mitigate the neurologic deficit.
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Received: 08 June 2017
Revised: 27 August 2017
Published: 04 January 2018
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[1] GUO M F,YU J Z,MA C G. Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia[J]. Folia Neuropathol,2011,49（2）：78-87.
[2] 王庄,邱彩霞,晏玉奎. 急性脑梗死患者早期神经功能恶化与阿司匹林抵抗的关系[J]. 预防医学,2017,29（1）：70-72.
[3] TODA N,OKAMURA T. Hyperhomocysteinemia impairs regional blood flow：involvements of endothelial and neuronal nitric oxide[J]. Pflugers Arch,2016,468（9）：1517-1525.
[4] JIN H,LIU T,WANG W X,et al. Protective effects of [Gly14]-Humanin on beta-amyloid-induced PC12 cell death by preventing mitochondrial dysfunction[J]. Neurochem Int,2010,56（3）：417-423.
[5] KAUR N,DHIMAN M,MANTHA AK. Ginkgolide B revamps neuroprotective role of apurinic/apyrimidinic endonuclease 1 and mitochondrial oxidative phosphorylation against Abeta-induced neurotoxicity in human neuroblastoma cells[J]. J Neurosci Res,2015,93（14）：938-947.
[6] XU X,CHUA C C,Gao J,et al. Humanin is a novel neuroprotective agent against stroke[J]. Stroke,2014,37（5）： 2613-2619.
[7] MIAO J,ZHANG W,YIN R,et al. S14G-Humanin ameliorates Abeta25-35-induced behavioral deficits by reducing neuroinflammatory responses and apoptosis in mice[J]. Neuropeptides,2008,42（5-6）：557-567.
[8] ZHANG W,MIAO J,HAO J,et al. Protective effect of S14G-humanin against beta-amyloid induced LTP inhibition in mouse hippocampal slices[J]. Peptides,2013,30（5）： 1197-1202.
[9] HASHIMOTO Y,NIIKURA T,TAJIMA H,et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta[J]. Proc Natl Acad Sci USA,2001,98（11）：6336-6341.
[10] LONGA E Z,WEINSTEIN P R,CARLSON S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke,1989,20（1）：84-91.
[11] SUN S,CHEN X,GAO Y,et al. Mn-SOD upregulation by electroacupuncture attenuates ischemic oxidative damage via CB1R-mediated STAT3 phosphorylation[J]. Mol Neurobiol,2016, 53（1）：331-343.
[12] XU H Y,CAI M,ZHANG X D. Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced diabetic retinopathy in rats[J]. Graefe’s Archive for Clinical and Experimental Ophthalmology,2015,253（9）：1485-1492.
[13] SOANE L,LI DAI W,FISKUM G,et al. Sulforaphane protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucose deprivation[J]. J Neurosci Res,2010,88（6）：1355-1363.
[14] 张片红,何芳,陈莹莹,等. 茶色素对脑缺血再灌注损伤大鼠一氧化氮合酶表达的影响[J]. 浙江预防医学,2011,23（8）：14-16,34.
[15] DANILOV C A,CHANDRASEKARAN K,RACZ J,et al. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation[J]. Glia,2009, 57（6）：645-656.
[16] WANG T,MIAO M,LI Y,et al. Effect of cynomorium flavonoids on morphology of perimenopausal depression mice model[J]. Saudi Pharmaceutical Journal,2016,24（3）：322-328. |
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