AMD3100 decreasing angiogenesis in rat models of cerebral chronic hypoperfusion by blocking SDF-1/CXCR4 pathway
10.3760/cma.j.issn.1671-8925.2015.08.002
- VernacularTitle:AMD3100通过阻断SDF-1/CXCR4通路减少脑慢性低灌注模型大鼠血管新生
- Author:
Lingyan WANG
1
;
Heng ZHANG
;
Shaolei GUO
;
Zhengsong HUANG
Author Information
1. 中山大学附属第一医院神经外科ICU
- Keywords:
Cerebral chronic hypoperfusion;
Stromal cells-derived factor-1α;
CXCR4;
Angiogenesis;
AMD3100
- From:
Chinese Journal of Neuromedicine
2015;14(8):764-769
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of ADM3100 on angiogenesis in rat models of cerebral chronic hypoperfusion (CCH) and its mechanism.Methods Thirty-six healthy female SD rats,weighting 200-250 g,were randomly divided in normal control group,CCH+AMD3100 group and CCH+saline group (n=12);rats in the CCH+AMD3100 group and CCH+saline group underwent end-to-side anastomosis between the left distal external jugular vein (EJV) and the ipsilateral common carotid artery,followed by ligation of the right vein draining the transverse sinus and bilateral external carotid arteries,and then,they were received intraperitoneal injection of 5 mg/ (kg·d) ADM3100 and physiological saline,respectively,for a consecutive 30 d.Rats were then scarified;microvessel density (MVD) was assessed based on immunohistochemistry of CD34,numbers of CXCR4 and CD45 double positive cells were confirmed by double immunofluorescence,and matrix metalloproteinases-9 (MMP-9) was evaluated by Western blotting.Results MVD was 61.82±19.83/mm2,89.50±23.61/mm2 and 121.70 ±31.12/mm2 in the normal control group,CCH+AMD3100 group and CCH+saline group,respectively;numbers of CXCR4 and CD45 double positive cells were 3.47±2.63,7.58±4.49 and 12.33± 6.11 per high power field (×200) in normal control group,CCH+AMD3100 group and CCH+saline group,respectively;significant differences between groups were noted (P＜0.05).As compared with the expression of MMP-9 in the normal control group,that in the CCH+AMD3100 group and CCH+saline group was significantly increased (0.009±0.003,0.151 ±0.058 and 0.325 ±0.068,P＜0.05).As compared with CCH+saline group,CCH+AMD3100 group had significantly smaller MVD and numbers of CXCR4 and CD45 double positive cells and lower MMP-9 level (P＜0.05).Conclusion AMD3100 will decrease angiogenesis in rat models of cerebral chronic hypoperfusion,which may be associated with inhibiting CXCR4+ CD45+ cells infiltration into cerebral tissue by blocking stromal cells-derived factor-1 α/CXCR4 signaling.
