Study of Angiogenesis Mechanisms of Vascular Endothelial Growth Factor Combined with Basic Fibroblast Growth Factor for Arteriosclerosis Obliterans of Rat Hind Limb_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGTing ¹ , WANGKai-feng ¹ , SUNYao ¹ , LIUYan-hui ¹ , WANGHan-rui ¹ , FANDong-xu ¹ , JINSong ¹ , DOUPeng-hui ¹ ,  LIUYan-dong ²

1. Department of Vascular Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi 154003, Heilongjiang Province, China;
2. Department of Vascular Surgery, The Fourth Daqing City Hospital, Daqing 163712, Heilongjiang Province, China;

Corresponding author：

LIUYan-dong, Email: liuyandong867719@126.com

Keywords：

Vascular endothelial growth factor; Basic fibroblast growth factor; Arteriosclerosis obliterans; Angiogenesis

DOI：

10.7507/1007-9424.20150239

Video：

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Objective To investigate the angiogenesis mechanisms of vascular endothelial growth factor (VEGF) combined with basic fibroblast growth factor (bFGF) for arteriosclerosis obliterans of rat hind limb. Methods The models of hind limb arteriosclerosis obliterans of 60 male SD rats were established and randomly divided into four groups:normal saline (NS) group, VEGF group, bFGF group, and VEGF+bFGF group. The saline 1 mL and 100μg/L rhVEGF 1 mL were respectively injected into the abdominal cavity on every other day in the NS group and VEGF group. The 100μg/L rhbFGF 1 mL was multiply injected into the hind limb medial vastus muscle in the bFGF group. The 100μg/L rhVEGF 1 mL and 100μg/L rhbFGF 1 mL were respectively injected into the abdominal cavity and the hind limb medial vastus muscle on every other day in the VEGF+bFGF group. The angiogenesis of rat hind limb arteriosclerosis obliterans was observed on day 30 by digital subtraction angiography (DSA). The VEGF and bFGF protein and mRNA expressions in the hind limb medial vastus muscle tissues were tested by the Western blot and RT-PCR methods respectively. Results ①The number of new collateral vessel in the VEGF+bFGF group was significantly more than that in the bFGF group (P < 0.05), VEGF group (P < 0.05), and NS group (P < 0.001), which in the VEGF group or bFGF group was significantly more than that in the NS group (P < 0.001), and which had no significant difference between the VEGF group and bFGF group (P > 0.05).②The protein and mRNA expressions of VEGF and bFGF in the VEGF+bFGF group were significantly higher than those in the bFGF group (P < 0.001), VEGF group (P < 0.001), and NS group (P < 0.001), which in the VEGF and bFGF were significantly higher than those in the NS group (P < 0.001), which had no significant difference between the VEGF group and bFGF group (P > 0.05). Conclusions VEGF and bFGF in combination could increase the expressions of VEGF and bFGF in the rat hind limb ischemia region tissue and promote vascular endothelial cell proliferation and differentiation, and capillary sprouting growth, make angiogenesis of ischemic area, it is provided a new clinical treatment of peripheral arterial disease.

Citation： YANGTing, WANGKai-feng, SUNYao, LIUYan-hui, WANGHan-rui, FANDong-xu, JINSong, DOUPeng-hui, LIUYan-dong. Study of Angiogenesis Mechanisms of Vascular Endothelial Growth Factor Combined with Basic Fibroblast Growth Factor for Arteriosclerosis Obliterans of Rat Hind Limb. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(8): 917-921. doi: 10.7507/1007-9424.20150239 Copy

1.	苏永才, 张小乐, 冯新武, 等.下肢动脉硬化闭塞症介入诊疗术的临床应用.罕少疾病杂志, 2014, 21(2):40-42.
2.	陈长广.腔内介入治疗下肢动脉硬化闭塞症的临床效果分析.中国当代医药, 2014, 21(14):67-68, 72.
3.	吴毅琴, 蔡承哲, 吕敏清.前列地尔联合阿托伐他汀治疗下肢动脉硬化闭塞症的临床研究.中外医学研究, 2014, 12(20):53-53, 54.
4.	李英莎, 赵志钢, 何洪波, 等.下肢动脉硬化闭塞症介入治疗效果及其影响因素分析.第三军医大学学报, 2013, 35(8):789-792.
5.	Claesson K, Kölbel T, Acosta S. Role of endovascular intervention in patients with diabetic foot ulcer and concomitant peripheral arterial disease. Int Angiol, 2011, 30(4):349-358.
6.	Gu YQ, Zhang J, Qi LX, et al. Surgical treatment of 82 patients with diabetic lower limb ischemia by distal arterial bypass. Chin Med J, 2007, 120(2):106-109.
7.	谷涌泉, 张建, 汪忠镐.膝下动脉缺血性病变腔内治疗技术的进展.中华外科杂志, 2012, 50(1):4-6.
8.	谷涌泉.下肢动脉硬化闭塞症腔内治疗的新进展.中国普通外科杂志, 2014, 23(6):719-723.
9.	谷涌泉, 郭连瑞, 张建, 等.自体骨髓干细胞移植治疗严重下肢缺血1例.中国实用外科杂志, 2003, 23(11):35, 72.
10.	Gu YQ, Zhang J, Guo LR, et al. Transplantation of autologous bone marrow mononuclear cells for patients with lower limb ischemia. Chin Med J, 2008, 121(11):963-967.
11.	栗力.下肢动脉硬化闭塞症术后再闭塞的腔内治疗.中国血管外科杂志:电子版, 2014, 6(2):68-70.
12.	Poldervaart MT, Gremmels H, van Deventer K, et al. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaf-folds with defined architecture. J Control Release, 2014, 184:58-66.
13.	Isner JM, Asahara T. Angiogenesis and vasculogenesis as thera-peutic strategies for postnatal neovascularization. J Clin Invest, 1999, 103(9):1231-1236.
14.	Lee KY, Peters MC, Anderson KW, et al. Controlled growth factor release from synthetic xtracel ular matrices. Nature, 2000, 408 (6815):998-1000.
15.	Richardson TP, Peters MC, Ennett AB, et al. Polymeric system for dual growth factor delivery. Nat Biotechnol, 2001, 19(11):1029-1034.
16.	Lui KO. VEGF-A:the inductive angiogenic factor for development, regeneration and function of pancreatic beta cells. Curr Stem Cell Res Ther, 2014, 9(5):396-400.
17.	Shibuya M. VEGF-VEGFR signals in heath and disease. Biomol Ther (Seoul), 2014, 22(1):1-9.
18.	李占武, 王利, 李方毅, 等.局部缓释血管内皮生长因子促进肠吻合口愈合的研究.中国普外基础与临床杂志, 2010, 17(11):1141-1145.
19.	Unger EF, Banai S, Shou M, et al. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol, 1994, 266(4 Pt 2):H1588-H1595.
20.	Fernandez B, Buehler A, Wolfram S, et al. Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching. Circ Res, 2000, 87(3):207-213.
21.	金松, 王瀚锐, 刘彦东, 等.碱性成纤维生长因子与血管内皮生长因子联合对大鼠后肢动脉硬化闭塞血管再生作用机制的研究.中国医药指南, 2013, 11(9):404-406.
22.	涂兵, 金立人.血管内皮细胞生长因子及有关肢体缺血基因治疗的研究进展.中国普外基础与临床杂志, 2000, 7(3):202-204.
23.	Buchberger B, Follmann M, Freyer D, et al. The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers. GMS Health Technol Assess, 2010, 6:Doc12.
24.	Han KY, Fahd DC, Tshionyi M, et al. MT1-MMP modulates bFGF-induced VEGF-A expression in corneal fibroblasts. Protein Pept Lett, 2012, 19(12):1334-1339.
25.	Zheng K, Mei B. Effects of exogenous sonic hedgehog peptide on proliferation, adhesion, migration of endothelial progenitor cells from peripheral blood. J Huazhong Uni Sci Techy (Medical Sciences), 2013, 33(3):335-338.
26.	Sufen G, Xianghong Y, Yongxia C, et al. bFGF and PDGF-BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells. Cell Biol Int, 2011, 35(5):545-551.
27.	Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of ph VEGF165 after intramuscular transfer promotes collateral vessel development in patients with critical ischemia. Circulation, 2000, 97(12):1114-1123.

1. 苏永才, 张小乐, 冯新武, 等.下肢动脉硬化闭塞症介入诊疗术的临床应用.罕少疾病杂志, 2014, 21(2):40-42.
2. 陈长广.腔内介入治疗下肢动脉硬化闭塞症的临床效果分析.中国当代医药, 2014, 21(14):67-68, 72.
3. 吴毅琴, 蔡承哲, 吕敏清.前列地尔联合阿托伐他汀治疗下肢动脉硬化闭塞症的临床研究.中外医学研究, 2014, 12(20):53-53, 54.
4. 李英莎, 赵志钢, 何洪波, 等.下肢动脉硬化闭塞症介入治疗效果及其影响因素分析.第三军医大学学报, 2013, 35(8):789-792.
5. Claesson K, Kölbel T, Acosta S. Role of endovascular intervention in patients with diabetic foot ulcer and concomitant peripheral arterial disease. Int Angiol, 2011, 30(4):349-358.
6. Gu YQ, Zhang J, Qi LX, et al. Surgical treatment of 82 patients with diabetic lower limb ischemia by distal arterial bypass. Chin Med J, 2007, 120(2):106-109.
7. 谷涌泉, 张建, 汪忠镐.膝下动脉缺血性病变腔内治疗技术的进展.中华外科杂志, 2012, 50(1):4-6.
8. 谷涌泉.下肢动脉硬化闭塞症腔内治疗的新进展.中国普通外科杂志, 2014, 23(6):719-723.
9. 谷涌泉, 郭连瑞, 张建, 等.自体骨髓干细胞移植治疗严重下肢缺血1例.中国实用外科杂志, 2003, 23(11):35, 72.
10. Gu YQ, Zhang J, Guo LR, et al. Transplantation of autologous bone marrow mononuclear cells for patients with lower limb ischemia. Chin Med J, 2008, 121(11):963-967.
11. 栗力.下肢动脉硬化闭塞症术后再闭塞的腔内治疗.中国血管外科杂志:电子版, 2014, 6(2):68-70.
12. Poldervaart MT, Gremmels H, van Deventer K, et al. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaf-folds with defined architecture. J Control Release, 2014, 184:58-66.
13. Isner JM, Asahara T. Angiogenesis and vasculogenesis as thera-peutic strategies for postnatal neovascularization. J Clin Invest, 1999, 103(9):1231-1236.
14. Lee KY, Peters MC, Anderson KW, et al. Controlled growth factor release from synthetic xtracel ular matrices. Nature, 2000, 408 (6815):998-1000.
15. Richardson TP, Peters MC, Ennett AB, et al. Polymeric system for dual growth factor delivery. Nat Biotechnol, 2001, 19(11):1029-1034.
16. Lui KO. VEGF-A:the inductive angiogenic factor for development, regeneration and function of pancreatic beta cells. Curr Stem Cell Res Ther, 2014, 9(5):396-400.
17. Shibuya M. VEGF-VEGFR signals in heath and disease. Biomol Ther (Seoul), 2014, 22(1):1-9.
18. 李占武, 王利, 李方毅, 等.局部缓释血管内皮生长因子促进肠吻合口愈合的研究.中国普外基础与临床杂志, 2010, 17(11):1141-1145.
19. Unger EF, Banai S, Shou M, et al. Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. Am J Physiol, 1994, 266(4 Pt 2):H1588-H1595.
20. Fernandez B, Buehler A, Wolfram S, et al. Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching. Circ Res, 2000, 87(3):207-213.
21. 金松, 王瀚锐, 刘彦东, 等.碱性成纤维生长因子与血管内皮生长因子联合对大鼠后肢动脉硬化闭塞血管再生作用机制的研究.中国医药指南, 2013, 11(9):404-406.
22. 涂兵, 金立人.血管内皮细胞生长因子及有关肢体缺血基因治疗的研究进展.中国普外基础与临床杂志, 2000, 7(3):202-204.
23. Buchberger B, Follmann M, Freyer D, et al. The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers. GMS Health Technol Assess, 2010, 6:Doc12.
24. Han KY, Fahd DC, Tshionyi M, et al. MT1-MMP modulates bFGF-induced VEGF-A expression in corneal fibroblasts. Protein Pept Lett, 2012, 19(12):1334-1339.
25. Zheng K, Mei B. Effects of exogenous sonic hedgehog peptide on proliferation, adhesion, migration of endothelial progenitor cells from peripheral blood. J Huazhong Uni Sci Techy (Medical Sciences), 2013, 33(3):335-338.
26. Sufen G, Xianghong Y, Yongxia C, et al. bFGF and PDGF-BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells. Cell Biol Int, 2011, 35(5):545-551.
27. Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of ph VEGF165 after intramuscular transfer promotes collateral vessel development in patients with critical ischemia. Circulation, 2000, 97(12):1114-1123.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of Angiogenesis Mechanisms of Vascular Endothelial Growth Factor Combined with Basic Fibroblast Growth Factor for Arteriosclerosis Obliterans of Rat Hind Limb

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