Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

被引:27
作者
Zhu, Haibo [1 ,3 ]
He, Jie [4 ]
Ye, Liang [1 ,3 ]
Lin, Fei [4 ]
Hou, Jian [4 ]
Zhong, Yan [4 ]
Jiang, Wanglin [2 ]
机构
[1] Binzhou Med Univ, Sch Publ Hlth & Management, Yantai 264003, Peoples R China
[2] Binzhou Med Univ, Sch Pharmaceut Sci, Inst Mat Med, Yantai 264003, Peoples R China
[3] Binzhou Med Univ, Inst Toxicol, Yantai 264003, Peoples R China
[4] Luye Pharma Grp Ltd, State Key Lab Long Acting Targeting Drug Delivery, Yantai 264003, Peoples R China
基金
中国国家自然科学基金;
关键词
Curculigoside A; Cerebral ischemia; Angiogenesis; Vascular endothelial growth factor; Blood-brain barrier; Wnt5a/beta-catenin; ENDOTHELIAL-CELLS; PROMOTES ANGIOGENESIS; IN-VITRO; GROWTH; PATHWAY; EXPRESSION; NEOVASCULARIZATION; PROLIFERATION; ACTIVATION; RECOVERY;
D O I
10.1016/j.taap.2015.08.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/beta-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood-brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Angl and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Angl and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/beta-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Angl and Tie-2 expression. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:313 / 321
页数:9
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