胸腺素β4通过提高Akt磷酸化促进局灶脑缺血/再灌注大鼠大脑皮质eNOS和CD31表达

基础医学与临床 ›› 2014, Vol. 34 ›› Issue (7): 921-926.

胸腺素β4通过提高Akt磷酸化促进局灶脑缺血/再灌注大鼠大脑皮质eNOS和CD31表达

庞月珊¹,罗勇²,谢宸宸¹,李满¹,陈瑞芳²,汶海琪¹

1. 重庆医科大学附属第一医院
2. 重庆医科大学附属第一医院神经内科

收稿日期:2013-08-05 修回日期:2013-11-25 出版日期:2014-07-05 发布日期:2014-06-24
通讯作者: 罗勇 E-mail:luoyong1998@163.com
基金资助:
教育部“高等学校博士学科点专项科研基金”联合资助课题;重庆市卫生局中医药科研项目;重庆市卫生局中医药重点科技项目

Thymosinβ4 improves CD31 and eNOS expression in rat cerebral cortex after focal cerebral ischemia/reperfusion by up-regulation phosphorylation level of Akt

Received:2013-08-05 Revised:2013-11-25 Online:2014-07-05 Published:2014-06-24

摘要/Abstract

摘要： 目的探讨胸腺素β4（Tβ4）对局灶脑缺血/再灌注大鼠大脑皮质血管再生影响及其机制。方法用线栓法制备大鼠局灶脑缺血/再灌注模型。将大鼠随机分为假手术组（S组）、模型组（IR组）、Tβ4组（IRT组）、Tβ4+LY294002组（IRTL组）、0.9%氯化钠注射液组（IRN组），缺血2h后把IR、IRN和IRT组分为3d和7d两亚组。Western blot检测Akt磷酸化水平和eNOS蛋白表达；免疫组化检测Tβ4和CD31蛋白表达；荧光定量PCR检测eNOS、SDF-1及CXCR4 mRNA表达；Longa法检测神经功能。结果与IRN组相比，IRT 3d Tβ4蛋白表达显著增多（P<0.01）；与IRN组比较，IRT 3d和7d Akt磷酸化水平和eNOS蛋白显著增高（P<0.05），但IRTL组与其比较p-Akt和eNOS蛋白表达显著减少（P<0.01）；与IRN组比较，IRT 3d和7d eNOS、SDF-1和CXCR4 mRNA表达显著升高（P<0.05）；与IRN组比较，IRT 3d和7d组微血管密度显著增高（P<0.05），大鼠神经功能缺损在第7天改善最明显（P<0.05）。结论 Tβ4可能通过提高局灶脑缺血/再灌注大鼠大脑皮质Akt磷酸化水平、eNOS基因和蛋白的表达，促进大鼠大脑皮质缺血半暗带血管再生和神经功能恢复。

关键词: 胸腺素β4, 局灶脑缺血/再灌注, 血管再生, eNOS, CD31, SDF-1/CXCR4, PI3K/Akt

Abstract: Objective To investigate the effect and mechanism of Thymosin beta4(Tβ4) on angiogenesis in rat cerebral cortex after focal cerebral ischemia/reperfusion. Methods Rats were randomly divided into sham group(S), model group(IR), Tβ4 group(IRT), Tβ4+LY294002 group(IRTL), 0.9% sodium chloride injection group(IRN). The focal ischemia/reperfusion rat model was established by filament occluding the right middle cerebral artery for 2 hours. Rats were divided into 3 and 7 day subgroups in IR、IRN and IRT group. The protein expression of eNOS、p-Akt and Akt were detected by western blotting. Immunohistochemical method was selected to detect the expression of Tβ4 and CD31. The mRNA expression of eNOS、SDF-1 and CXCR4 were tested by fluorogenic quantitative PCR. Longa score was selected to evaluate neurobehavioral. Results Compare with IRN group, the protein expression of Tβ4 increased significantly at IRT 3 day(P<0.01); compared with IRN group, the protein expression of eNOS、p-Akt increased significantly at IRT 3 and 7 day (p<0.05), but in IRTL group they reduced significantly (P<0.01); compare with IRN group , the mRNA expression of eNOS、SDF-1 and CXCR4 were increased significantly at IRT 3 and 7 day (p<0.05); The number of CD31 postive micrangium increased significantly at IRT 3 and 7 day (P<0.05) and the neural function recovery significantly at IRT 7 day (p<0.05). Conclusion Tβ4 may promotes angiogenesis and behavioral recovery by increasing p-Akt and eNOS expression in a rat model of focal cerebral ischemia/reperfusion.

Key words: Thymosinβ4, focal cerebral ischemia/reperfusion, angiogenesis, eNOS, CD31, SDF-1/CXCR4, PI3K/Akt

中图分类号:

R743.33

庞月珊罗勇谢宸宸李满陈瑞芳汶海琪. 胸腺素β4通过提高Akt磷酸化促进局灶脑缺血/再灌注大鼠大脑皮质eNOS和CD31表达[J]. 基础医学与临床, 2014, 34(7): 921-926.

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