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.	蘇永才, 張小樂, 馮新武, 等.下肢動脈硬化閉塞癥介入診療術的臨床應用.罕少疾病雜志, 2014, 21(2):40-42.
2.	陳長廣.腔內介入治療下肢動脈硬化閉塞癥的臨床效果分析.中國當代醫藥, 2014, 21(14):67-68, 72.
3.	吳毅琴, 蔡承哲, 呂敏清.前列地爾聯合阿托伐他汀治療下肢動脈硬化閉塞癥的臨床研究.中外醫學研究, 2014, 12(20):53-53, 54.
4.	李英莎, 趙志鋼, 何洪波, 等.下肢動脈硬化閉塞癥介入治療效果及其影響因素分析.第三軍醫大學學報, 2013, 35(8):789-792.
5.	Claesson K, K?lbel 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, 張建, 汪忠鎬.膝下動脈缺血性病變腔內治療技術的進展.中華外科雜志, 2012, 50(1):4-6.
8.	谷涌泉.下肢動脈硬化閉塞癥腔內治療的新進展.中國普通外科雜志, 2014, 23(6):719-723.
9.	谷涌泉, 郭連瑞, 張建, 等.自體骨髓干細胞移植治療嚴重下肢缺血1例.中國實用外科雜志, 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.下肢動脈硬化閉塞癥術后再閉塞的腔內治療.中國血管外科雜志:電子版, 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.局部緩釋血管內皮生長因子促進腸吻合口愈合的研究.中國普外基礎與臨床雜志, 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, 王瀚銳, 劉彥東, 等.堿性成纖維生長因子與血管內皮生長因子聯合對大鼠后肢動脈硬化閉塞血管再生作用機制的研究.中國醫藥指南, 2013, 11(9):404-406.
22.	涂兵, 金立人.血管內皮細胞生長因子及有關肢體缺血基因治療的研究進展.中國普外基礎與臨床雜志, 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. 蘇永才, 張小樂, 馮新武, 等.下肢動脈硬化閉塞癥介入診療術的臨床應用.罕少疾病雜志, 2014, 21(2):40-42.
2. 陳長廣.腔內介入治療下肢動脈硬化閉塞癥的臨床效果分析.中國當代醫藥, 2014, 21(14):67-68, 72.
3. 吳毅琴, 蔡承哲, 呂敏清.前列地爾聯合阿托伐他汀治療下肢動脈硬化閉塞癥的臨床研究.中外醫學研究, 2014, 12(20):53-53, 54.
4. 李英莎, 趙志鋼, 何洪波, 等.下肢動脈硬化閉塞癥介入治療效果及其影響因素分析.第三軍醫大學學報, 2013, 35(8):789-792.
5. Claesson K, K?lbel 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, 張建, 汪忠鎬.膝下動脈缺血性病變腔內治療技術的進展.中華外科雜志, 2012, 50(1):4-6.
8. 谷涌泉.下肢動脈硬化閉塞癥腔內治療的新進展.中國普通外科雜志, 2014, 23(6):719-723.
9. 谷涌泉, 郭連瑞, 張建, 等.自體骨髓干細胞移植治療嚴重下肢缺血1例.中國實用外科雜志, 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.下肢動脈硬化閉塞癥術后再閉塞的腔內治療.中國血管外科雜志:電子版, 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.局部緩釋血管內皮生長因子促進腸吻合口愈合的研究.中國普外基礎與臨床雜志, 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, 王瀚銳, 劉彥東, 等.堿性成纖維生長因子與血管內皮生長因子聯合對大鼠后肢動脈硬化閉塞血管再生作用機制的研究.中國醫藥指南, 2013, 11(9):404-406.
22. 涂兵, 金立人.血管內皮細胞生長因子及有關肢體缺血基因治療的研究進展.中國普外基礎與臨床雜志, 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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