Study of Accelerating Effect of Local Delayed Releasing Vascular Endothelial Growth Factor on Healing of Intestinal Anastomotic Stoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Zhanwu , WANG Li , LI Fangyi , MA Sufang , LIU Jinhua , LIU Tianqing , FAN Minghui.

Department of General Surgery, Friendship Hospital of Dalian, Dalian 116001, Liaoning Province, China;

Corresponding author：

Keywords：

Vascular endothelial growth factor; Fibrin glue; Intestinal anastomosis; Stomal leak

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Objective To investigate the effect of local delayed releasing vascular endothelial growth factor (VEGF) on accelerating healing of intestinal anastomotic stoma. Methods An intra-abdominal infection modal of rabbit was established by artificial appendix perforation, and excision and anastomosis of terminal ileum were subsequently performed after 12 h. The animals were divided into four groups (32 for each group) with different reagents on anastomotic surface: control group, fibrin glue group (FG group), VEGF group, and VEGF＋FG group. The incidence of stomal leak, anastomosic bursting pressure, hydroxyproline content, and expression of VEGF in cured stoma tissue were measured respectively on day 3, 5, 7 and 14 after operation. Results The total incidence rate of leakage was lower in FG group and VEGF group than that in control group, but there was no statistical significance （P gt;0.05）. The incidence rate was significantly lower in FG＋VEGF group than that in control group （P lt;0.05）. On day 14 postoperatively, the bursting pressure of anastomotic stoma, hydroxyproline content, and positive cell expression rate of VEGF protein (except VEGF group) were significantly increased in FG＋VEGF group than those in other three groups （P lt;0.05, P lt;0.01）. Conclusion Local delayed release of VEGF by fibrin glue can improve the healing of intestinal anastomotic stoma and reduce the incidence of stomal leak.

Citation： LI Zhanwu,WANG Li,LI Fangyi,MA Sufang,LIU Jinhua,LIU Tianqing,FAN Minghui.. Study of Accelerating Effect of Local Delayed Releasing Vascular Endothelial Growth Factor on Healing of Intestinal Anastomotic Stoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(11): 1141-1146. doi: Copy

1.	Golub R, Golub RW, Cantu R Jr, et al. A multivariate analysis of factors contributing to leakage of intestinal anastomoses [J]. J Am Coll Surg, 1997; 184(4): 364-372.
2.	Hgstrm H, Jiborn H, Zederfeldt B, et al. Influence of intraperitoneal Escherichia coli with septicemia on the healing of colonic anastomoses and skin wounds. An experimental study in the rat [J]. Eur Surg Res, 1985; 17(2): 128-132.
3.	Irvin TT. Collagen metabolism in infected colonic anastomoses [J]. Surg Gynecol Obstet, 1976; 143(2): 220-224.
4.	江涛，黎介寿. 纤维蛋白胶和生长激素促进腹腔感染条件下大鼠肠吻合口愈合的研究 [J]. 中华普通外科杂志, 2002; 17(3): 173-176.
5.	詹利永, 王敏, 陆伯豪, 等. 医用胶减少胃癌术后腹腔渗出的随机对照研究 [J]. 中华胃肠外科杂志， 2005; 8（1）: 43-45.
6.	李幼生, 鲍扬, 江涛, 等. 生长激素、纤维蛋白胶促进腹腔感染大鼠肠吻合口愈合的动态研究 [J]. 肠外与肠内营养, 2004; 11(3): 147-150.
7.	Houston KA, Rotstein OD. Fibrin sealant in high-risk colonic anastomoses [J]. Arch Surg, 1988; 123(2): 230-234.
8.	Shima DT, Deutsch U, D’Amore PA. Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability [J]. FEBS Lett, 1995; 370(3): 203-208.
9.	杨毅军，石景森. 血管内皮生长因子与肿瘤血管生成 [J]. 中国普外基础与临床杂志， 2001; 8（3）： 205-207.
10.	郑振华, 徐良, 范西红, 等. 联合应用血管内皮生长因子治疗急性肢体缺血的研究 [J]. 中国现代医学杂志, 2003; 13(12): 12-14.
11.	张聚良，王岭，晋援朝, 等. 肉芽组织血管生成过程中血管内皮生长因子及β3整合素的表达 [J]. 中国普外基础与临床杂志， 2001; 8(6)： 378-380.
12.	Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis [J]. J Clin Invest, 1989; 84(5): 1470-1478.
13.	Eming SA, Medalie DA, Tompkins RG, et al. Genetically modified human keratinocytes overexpressing PDGF-A enhance the performance of a composite skin graft [J]. Hum Gene Ther, 1998; 9(4): 529-539.
14.	Padubidri A, Browne E Jr. Effect of vascular endothelial growth factor (VEGF) on survival of random extension of axial pattern skin flaps in the rat [J]. Ann Plast Surg, 1996; 37(6): 604-611.
15.	Pu LQ, Sniderman AD, Arekat Z, et al. Angiogenic growth factor and revascularization of the ischemic limb: evaluation in a rabbit model [J]. J Surg Res, 1993; 54(6): 575-583.
16.	Shireman PK, Greisler HP. Mitogenicity and release of vascular endothelial growth factor with and without heparin from fibrin glue [J]. J Vasc Surg, 2000; 31(5): 936-943.
17.	Spotnitz WD, Prabhu R. Fibrin sealant tissue adhesive-review and update [J]. J Long Term Eff Med Implants, 2005; 15(3): 245-270.
18.	Cruysberg LP, Nuijts RM, Gilbert JA, et al. In vitro sustained human transscleral drug delivery of fluorescein-labeled dexamethasone and methotrexate with fibrin sealant [J]. Curr Eye Res, 2005; 30(8): 653-660.
19.	Simpson AE, Gilbert JA, Rudnick DE, et al. Transscleral diffusion of carboplatin: an in vitro and in vivo study [J]. Arch Ophthalmol, 2002; 120(8): 1069-1074.
20.	Moon MC, Molnar K, Yau L, et al. Perivascular delivery of losartan with surgical fibrin glue prevents neointimal hyperplasia after arterial injury [J]. J Vasc Surg, 2004; 40(1): 130-137.
21.	Erzurum VZ, Bian JF, Husak VA, et al. R136K fibroblast growth factor-1 mutant induces heparin-independent migration of endothelial cells through fibrin glue [J]. J Vasc Surg, 2003; 37(5): 1075-1081.
22.	马西. 纤维蛋白形成与降解 [J]. 微循环学杂志， 2002; 12(4): 42-44.
23.	高秋明，刘兴炎，陈克明. 纤维蛋白凝胶复合骨形态发生蛋白及庆大霉素缓释药物的制备及其体内动力学研究 [J]. 西北国防医学杂志， 2002; 23（1）： 48-50.
24.	Qu W, Muneshige H, Ikuta Y. An absorbable pinned-ring device for microvascular anastomosis of vein grafts: experimental studies [J]. Microsurgery, 1999; 19(3): 128-134.
25.	黄晨昱，沈祖尧. 血管内皮细胞生长因子和碱性成纤维细胞生长因子加速预构扩张皮瓣成熟的研究 [J]. 中国修复重建外科杂志， 2003; 17（4）： 293-297.
26.	边杰芳，马中，姚青, 等. 纤维蛋白胶释放VEGF加速损伤动脉血管内皮化的实验研究 [J]. 中华普通外科杂志， 2005; 20（10）： 663-665.

1. Golub R, Golub RW, Cantu R Jr, et al. A multivariate analysis of factors contributing to leakage of intestinal anastomoses [J]. J Am Coll Surg, 1997; 184(4): 364-372.
2. Hgstrm H, Jiborn H, Zederfeldt B, et al. Influence of intraperitoneal Escherichia coli with septicemia on the healing of colonic anastomoses and skin wounds. An experimental study in the rat [J]. Eur Surg Res, 1985; 17(2): 128-132.
3. Irvin TT. Collagen metabolism in infected colonic anastomoses [J]. Surg Gynecol Obstet, 1976; 143(2): 220-224.
4. 江涛，黎介寿. 纤维蛋白胶和生长激素促进腹腔感染条件下大鼠肠吻合口愈合的研究 [J]. 中华普通外科杂志, 2002; 17(3): 173-176.
5. 詹利永, 王敏, 陆伯豪, 等. 医用胶减少胃癌术后腹腔渗出的随机对照研究 [J]. 中华胃肠外科杂志， 2005; 8（1）: 43-45.
6. 李幼生, 鲍扬, 江涛, 等. 生长激素、纤维蛋白胶促进腹腔感染大鼠肠吻合口愈合的动态研究 [J]. 肠外与肠内营养, 2004; 11(3): 147-150.
7. Houston KA, Rotstein OD. Fibrin sealant in high-risk colonic anastomoses [J]. Arch Surg, 1988; 123(2): 230-234.
8. Shima DT, Deutsch U, D’Amore PA. Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability [J]. FEBS Lett, 1995; 370(3): 203-208.
9. 杨毅军，石景森. 血管内皮生长因子与肿瘤血管生成 [J]. 中国普外基础与临床杂志， 2001; 8（3）： 205-207.
10. 郑振华, 徐良, 范西红, 等. 联合应用血管内皮生长因子治疗急性肢体缺血的研究 [J]. 中国现代医学杂志, 2003; 13(12): 12-14.
11. 张聚良，王岭，晋援朝, 等. 肉芽组织血管生成过程中血管内皮生长因子及β3整合素的表达 [J]. 中国普外基础与临床杂志， 2001; 8(6)： 378-380.
12. Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis [J]. J Clin Invest, 1989; 84(5): 1470-1478.
13. Eming SA, Medalie DA, Tompkins RG, et al. Genetically modified human keratinocytes overexpressing PDGF-A enhance the performance of a composite skin graft [J]. Hum Gene Ther, 1998; 9(4): 529-539.
14. Padubidri A, Browne E Jr. Effect of vascular endothelial growth factor (VEGF) on survival of random extension of axial pattern skin flaps in the rat [J]. Ann Plast Surg, 1996; 37(6): 604-611.
15. Pu LQ, Sniderman AD, Arekat Z, et al. Angiogenic growth factor and revascularization of the ischemic limb: evaluation in a rabbit model [J]. J Surg Res, 1993; 54(6): 575-583.
16. Shireman PK, Greisler HP. Mitogenicity and release of vascular endothelial growth factor with and without heparin from fibrin glue [J]. J Vasc Surg, 2000; 31(5): 936-943.
17. Spotnitz WD, Prabhu R. Fibrin sealant tissue adhesive-review and update [J]. J Long Term Eff Med Implants, 2005; 15(3): 245-270.
18. Cruysberg LP, Nuijts RM, Gilbert JA, et al. In vitro sustained human transscleral drug delivery of fluorescein-labeled dexamethasone and methotrexate with fibrin sealant [J]. Curr Eye Res, 2005; 30(8): 653-660.
19. Simpson AE, Gilbert JA, Rudnick DE, et al. Transscleral diffusion of carboplatin: an in vitro and in vivo study [J]. Arch Ophthalmol, 2002; 120(8): 1069-1074.
20. Moon MC, Molnar K, Yau L, et al. Perivascular delivery of losartan with surgical fibrin glue prevents neointimal hyperplasia after arterial injury [J]. J Vasc Surg, 2004; 40(1): 130-137.
21. Erzurum VZ, Bian JF, Husak VA, et al. R136K fibroblast growth factor-1 mutant induces heparin-independent migration of endothelial cells through fibrin glue [J]. J Vasc Surg, 2003; 37(5): 1075-1081.
22. 马西. 纤维蛋白形成与降解 [J]. 微循环学杂志， 2002; 12(4): 42-44.
23. 高秋明，刘兴炎，陈克明. 纤维蛋白凝胶复合骨形态发生蛋白及庆大霉素缓释药物的制备及其体内动力学研究 [J]. 西北国防医学杂志， 2002; 23（1）： 48-50.
24. Qu W, Muneshige H, Ikuta Y. An absorbable pinned-ring device for microvascular anastomosis of vein grafts: experimental studies [J]. Microsurgery, 1999; 19(3): 128-134.
25. 黄晨昱，沈祖尧. 血管内皮细胞生长因子和碱性成纤维细胞生长因子加速预构扩张皮瓣成熟的研究 [J]. 中国修复重建外科杂志， 2003; 17（4）： 293-297.
26. 边杰芳，马中，姚青, 等. 纤维蛋白胶释放VEGF加速损伤动脉血管内皮化的实验研究 [J]. 中华普通外科杂志， 2005; 20（10）： 663-665.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study of Accelerating Effect of Local Delayed Releasing Vascular Endothelial Growth Factor on Healing of Intestinal Anastomotic Stoma

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