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胰高血糖素样肽1类似物利拉鲁肽延迟给药促进小鼠局灶性脑缺血后的血管生成

Delayed Administration of the Glucagon-Like Peptide 1 Analog Liraglutide Promoting Angiogenesis after Focal Cerebral Ischemia in Mice.

作者信息

Chen Yanxia, Zhang Xiangjian, He Junna, Xie Yanzhao, Yang Yang

机构信息

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, China.

出版信息

J Stroke Cerebrovasc Dis. 2018 May;27(5):1318-1325. doi: 10.1016/j.jstrokecerebrovasdis.2017.12.015. Epub 2018 Feb 1.

Abstract

BACKGROUND

Glucagon-like peptide 1 (GLP-1) analogs administered before or after cerebral ischemia have been shown to provide neuroprotection. Here, we explored whether delayed administration of a GLP-1 analog, liraglutide, could improve long-term functional recovery and promote angiogenesis after stroke.

MATERIALS AND METHODS

In the present study, mice were established as a focal cerebral cortical ischemia model and were intraperitoneally administered liraglutide or normal saline (NS) daily for 14 consecutive days, starting 1 day after cerebral ischemia. The neurological deficits were evaluated using rotarod test. The microvessel density (MVD) and endothelial cell (EC) proliferation were assessed by immunohistochemical staining. The expression of vascular endothelial growth factor (VEGF) was assessed by Western blot analysis.

RESULTS

Liraglutide significantly reduced infarct volume and improved the rotarod test scores, compared with mice treated with NS. Liraglutide also greatly increased the MVD and EC proliferation and simultaneously upregulated the expression of VEGF in the cerebral ischemic area.

CONCLUSIONS

These results demonstrated that liraglutide promoted angiogenesis and long-term recovery of cerebral ischemia through increasing the expression of VEGF.

摘要

背景

已表明在脑缺血之前或之后给予胰高血糖素样肽1(GLP-1)类似物可提供神经保护作用。在此,我们探讨了延迟给予GLP-1类似物利拉鲁肽是否能改善中风后的长期功能恢复并促进血管生成。

材料与方法

在本研究中,将小鼠建立为局灶性大脑皮质缺血模型,并在脑缺血后1天开始连续14天每天腹腔注射利拉鲁肽或生理盐水(NS)。使用转棒试验评估神经功能缺损。通过免疫组织化学染色评估微血管密度(MVD)和内皮细胞(EC)增殖。通过蛋白质印迹分析评估血管内皮生长因子(VEGF)的表达。

结果

与用NS治疗的小鼠相比,利拉鲁肽显著减小梗死体积并改善转棒试验评分。利拉鲁肽还极大地增加了MVD和EC增殖,并同时上调了脑缺血区域VEGF的表达。

结论

这些结果表明,利拉鲁肽通过增加VEGF的表达促进脑缺血后的血管生成和长期恢复。

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