[1]王晗 雷占翔 郭虹敏.Exendin-4对MCAO再灌注导致的脑缺血/再灌注损伤具有神经保护作用[J].卒中与神经疾病杂志,2020,27(05):576-579.[doi:10.3969/j.issn.1007-0478.2020.05.004]
 Wang Han*,Lei Zhanxiang*,Guo Hongmin..Neuroprotective effect of Exendin-4 on cerebral ischemia / reperfusion injury induced by MCAO reperfusion[J].Stroke and Nervous Diseases,2020,27(05):576-579.[doi:10.3969/j.issn.1007-0478.2020.05.004]
点击复制

Exendin-4对MCAO再灌注导致的脑缺血/再灌注损伤具有神经保护作用()
分享到:

《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第27卷
期数:
2020年05期
页码:
576-579
栏目:
论 著
出版日期:
2020-10-20

文章信息/Info

Title:
Neuroprotective effect of Exendin-4 on cerebral ischemia / reperfusion injury induced by MCAO reperfusion
文章编号:
1007-0478(2020)05-0576-04
作者:
王晗 雷占翔 郭虹敏
Author(s):
Wang Han* Lei Zhanxiang* Guo Hongmin.
*Department of Clinical Microbiology and Immunology, The 990th Hospital of PLA, Zhumadian Henan 463000
关键词:
Exendin-4 大脑中动脉闭塞再灌注 神经元 小胶质细胞 凋亡
Keywords:
Exendin-4 MCAO reperfusion Neuron Microglial cell Apoptosis
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2020.05.004
文献标志码:
A
摘要:
目的 探讨GLP-1受体激动剂Exendin-4腹腔给药对大脑中动脉闭塞(MCAO)再灌注所致大鼠脑缺血/再灌注损伤的神经保护作用。方法 SD大鼠术前1 h腹腔注射Exendin-4,MCAO再灌注24 h后进行神经功能缺损评分,TTC染色计算脑梗死体积,免疫荧光观察神经元和小胶质细胞生存数量及检测凋亡通路相关蛋白的相对表达水平。结果 Exendin-4能够保护由于MCAO再灌注后所致的脑缺血再灌注损伤,减少了脑梗死体积,降低皮层凋亡蛋白的相对表达水平,抑制神经元凋亡。结论 Exendin-4可以对MCAO再灌注所致脑缺血/再灌注损伤具有神经保护作用,该作用是通过抑制凋亡蛋白的产生,从而抑制细胞凋亡。
Abstract:
ObjectiveTo investigate the neuroprotective effect of exendin-4, a GLP-1 receptor agonist, on cerebral ischemia / reperfusion injury induced by middle cerebral artery occlusion(MCAO)reperfusion in rats.Methods SD rats were given exendin-4 intraperitoneally 1h before operation, and MCAO reperfusion injury was operated. Neuroprotective effect was valued after 24h of reperfusion through neurologic deficit score, infarct size, survival count of neuron and microglial. Infarct size was counted by TCC staining. Survival count of neuron and microglial cells were analyzed by immunofluorescence and the expression levels of correlative protein about apoptosis pathway were tested by western blot.Results Exendin-4 could protect the cerebral ischemia / reperfusion injury caused by MCAO reperfusion, reduce the infarct volume and the expression levels of apoptosis protein in cortex, and inhibit neuron apoptosis.Conclusion Exendin-4 had neuroprotective effect on cerebral ischemia / reperfusion injury induced by MCAO reperfusion, which could inhibit neuron apoptosis by inhibiting the production of apoptotic protein.

参考文献/References:

[1] Hao L,Zou Z,Tian H,et al.Stem cell-based therapies for ischemic stroke[OL].Biomed Res Int,2014.doi: 10.1155/2014/468748.
[2] Wang J,Huang Q,Ding J,et al.Elevated serum levels of brain-derived neurotrophic factor and miR-124 in acute ischemic strokepatients and the molecular mechanism[J].3 Biotech,2019,9(11):386.
[3] Khatri R,Mckinney AM,Swenson BA.Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke[J].Neurology,2012,79(13, 1):S52-S57.
[4] Zhang H,Meng J,Li X,et al.Pro-GLP-1,a pro-drug of GLP-1,is neuroprotective in cerebral ischemia[J].Eur J Pharm Sci,2015,5(70):82-91.
[5] Teramoto S,Miyamoto N,Yatomi KA,et al.Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia[J].Journal of Cerebral Blood Flow and Metabolism,2011,31(8):1696-1705.
[6] Deacon CF,Pridal L,Klarskov L,et al.Glucagon-like peptide 1 undergos differential tissue-specific metabolism in the anesthetized pig[J].Am J Physiol,1996,271(3):458-464.
[7] Nielsen LL,YoungAA,Parkes DG.Pharmacology of exenatide(synthetic exendin-4):a potential therapeutic for improved glycemic control of type 2 diabetes[J].Regul Pept,2004,117(2):77-88.
[8] Ma X,Meng J,Jia M,et al.Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats[J].J Bone Miner Res,2013,28(7):1641-1652.
[9] Mcbride DW,Zhang JH.Precision stroke animal models:the permanent MCAO model should be the primary model,not transient MCAO[OL].Transl Stroke Res[Z],2017.
[10] Bertilsson G,Patrone C,Zachrisson OA,et al.Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease[J].J Neurosci Res,2008,86(2):326-338.
[11] Harkavyi A,Abuirmeileh A,Lever R,et al.Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease[J].J Neuroinflammation,2008,doi:10.1186/1742-2094-5-19.
[12] Love S.Oxidative stress in brain ischemia[J].Brain Pathol,1999,9(1):119-131.
[13] Han L,Yu Y,Sun X,et al.Exendin-4 directly improves endothelial dysfunction in isolated aortas from obese rats through the cAMP or AMPK-eNOS pathways[J].Diabetes Res Clin Pract,2012,97(3):453-460.
[14] Liebner S,Corada M,Bangsow T,et al.Wnt/beta-catenin signaling controls development of the blood-brain barrier[J].J Cell Biol,2008,183(3):409-417.
[15] Moghaddam HK,Baluchnejadmojarad T,Roghani M,et al.Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats[J].Mol Neurobiol,2014,49(2):820-826.
[16] Briyal S SS,Ischemia Effects of Liraglutide in the Rat Brain Following Focal Cerebral Anti-apoptotic.Neuroscience[Z],2014.
[17] Guyton J,Jeon M,Brooks A.Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus[J].Am J Health Syst Pharm,2019,76(21):1739-1748.
[18] Meller R,Minami M,Cameron JA,et al.CREB-mediated Bcl-2 protein expression after ischemic preconditioning[J].J Cereb Blood Flow Metab,2005,25(2):234-246.
[19] Hockenbery DM,Oltvai ZN,Yin XM,et al.Bcl-2 functions in an antioxidant pathway to prevent apoptosis[J].Cell,1993,75(2):241-251.
[20] Chien CT,Ming JJ,Yc T,et al.Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats[J].J Cereb Blood Flow Metab,2015,35(11):1790-1803.

备注/Memo

备注/Memo:
(2019-12-25收稿)基金项目:山东省中医药科技发展计划项目(2019-0888)作者单位:463000 解放军第九九○医院检验病理科(王晗 雷占翔); 聊城市人民医院生殖医学科[郭虹敏(通信作者)]
更新日期/Last Update: 2020-10-20