• 大連市友誼醫(yī)院普外科(遼寧大連116001);

目的 探討應(yīng)用生物蛋白膠緩釋血管內(nèi)皮生長因子(VEGF)促進腸吻合口愈合的有效性。方法 通過在兔盲腸穿孔建立腹腔感染的動物模型,12 h后行腸切除及腸吻合。動物分成4組(每組32只),各組吻合口表面所涂試劑不同: 生理鹽水組、生物蛋白膠組、VEGF組及VEGF+生物蛋白膠組。于手術(shù)后第 3、5、7及14天統(tǒng)計各組吻合口漏發(fā)生情況,測量未發(fā)生吻合口漏的動物的吻合口破裂壓,檢測吻合口組織羥脯氨酸含量及VEGF表達情況。結(jié)果 生物蛋白膠組及VEGF組的吻合口漏總發(fā)生率低于對照組,但差異無統(tǒng)計學(xué)意義(P gt;0.05),而VEGF+生物蛋白膠組則明顯低于對照組(P lt;0.05)。至術(shù)后第14天,VEGF+生物蛋白膠組的吻合口破裂壓、吻合口組織羥脯氨酸含量及VEGF蛋白表達陽性細胞率(除VEGF組)均較其余3組明顯升高(P lt;0.05, P lt;0.01)。結(jié)論 應(yīng)用生物蛋白膠局部緩釋VEGF能夠促進腸吻合口愈合,降低吻合口漏的發(fā)生率。

引用本文: 李占武,王利,李方毅,馬素芳,劉金華,劉天卿,范明慧. 局部緩釋血管內(nèi)皮生長因子促進腸吻合口愈合的研究. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(11): 1141-1146. doi: 復(fù)制

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. 江濤, 黎介壽. 纖維蛋白膠和生長激素促進腹腔感染條件下大鼠腸吻合口愈合的研究 [J]. 中華普通外科雜志, 2002; 17(3): 173-176.
5. 詹利永, 王敏, 陸伯豪, 等. 醫(yī)用膠減少胃癌術(shù)后腹腔滲出的隨機對照研究 [J]. 中華胃腸外科雜志, 2005; 8(1): 43-45.
6. 李幼生, 鮑揚, 江濤, 等. 生長激素、纖維蛋白膠促進腹腔感染大鼠腸吻合口愈合的動態(tài)研究 [J]. 腸外與腸內(nèi)營養(yǎng), 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. 楊毅軍, 石景森. 血管內(nèi)皮生長因子與腫瘤血管生成 [J]. 中國普外基礎(chǔ)與臨床雜志, 2001; 8(3): 205-207.
10. 鄭振華, 徐良, 范西紅, 等. 聯(lián)合應(yīng)用血管內(nèi)皮生長因子治療急性肢體缺血的研究 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2003; 13(12): 12-14.
11. 張聚良, 王嶺, 晉援朝, 等. 肉芽組織血管生成過程中血管內(nèi)皮生長因子及β3整合素的表達 [J]. 中國普外基礎(chǔ)與臨床雜志, 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. 馬西. 纖維蛋白形成與降解 [J]. 微循環(huán)學(xué)雜志, 2002; 12(4): 42-44.
23. 高秋明, 劉興炎, 陳克明. 纖維蛋白凝膠復(fù)合骨形態(tài)發(fā)生蛋白及慶大霉素緩釋藥物的制備及其體內(nèi)動力學(xué)研究 [J]. 西北國防醫(yī)學(xué)雜志, 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. 黃晨昱, 沈祖堯. 血管內(nèi)皮細胞生長因子和堿性成纖維細胞生長因子加速預(yù)構(gòu)擴張皮瓣成熟的研究 [J]. 中國修復(fù)重建外科雜志, 2003; 17(4): 293-297.
26. 邊杰芳, 馬中, 姚青, 等. 纖維蛋白膠釋放VEGF加速損傷動脈血管內(nèi)皮化的實驗研究 [J]. 中華普通外科雜志, 2005; 20(10): 663-665.
  1. 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. 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. 3. Irvin TT. Collagen metabolism in infected colonic anastomoses [J]. Surg Gynecol Obstet, 1976; 143(2): 220-224.
  4. 4. 江濤, 黎介壽. 纖維蛋白膠和生長激素促進腹腔感染條件下大鼠腸吻合口愈合的研究 [J]. 中華普通外科雜志, 2002; 17(3): 173-176.
  5. 5. 詹利永, 王敏, 陸伯豪, 等. 醫(yī)用膠減少胃癌術(shù)后腹腔滲出的隨機對照研究 [J]. 中華胃腸外科雜志, 2005; 8(1): 43-45.
  6. 6. 李幼生, 鮑揚, 江濤, 等. 生長激素、纖維蛋白膠促進腹腔感染大鼠腸吻合口愈合的動態(tài)研究 [J]. 腸外與腸內(nèi)營養(yǎng), 2004; 11(3): 147-150.
  7. 7. Houston KA, Rotstein OD. Fibrin sealant in high-risk colonic anastomoses [J]. Arch Surg, 1988; 123(2): 230-234.
  8. 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. 9. 楊毅軍, 石景森. 血管內(nèi)皮生長因子與腫瘤血管生成 [J]. 中國普外基礎(chǔ)與臨床雜志, 2001; 8(3): 205-207.
  10. 10. 鄭振華, 徐良, 范西紅, 等. 聯(lián)合應(yīng)用血管內(nèi)皮生長因子治療急性肢體缺血的研究 [J]. 中國現(xiàn)代醫(yī)學(xué)雜志, 2003; 13(12): 12-14.
  11. 11. 張聚良, 王嶺, 晉援朝, 等. 肉芽組織血管生成過程中血管內(nèi)皮生長因子及β3整合素的表達 [J]. 中國普外基礎(chǔ)與臨床雜志, 2001; 8(6): 378-380.
  12. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22. 馬西. 纖維蛋白形成與降解 [J]. 微循環(huán)學(xué)雜志, 2002; 12(4): 42-44.
  23. 23. 高秋明, 劉興炎, 陳克明. 纖維蛋白凝膠復(fù)合骨形態(tài)發(fā)生蛋白及慶大霉素緩釋藥物的制備及其體內(nèi)動力學(xué)研究 [J]. 西北國防醫(yī)學(xué)雜志, 2002; 23(1): 48-50.
  24. 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. 25. 黃晨昱, 沈祖堯. 血管內(nèi)皮細胞生長因子和堿性成纖維細胞生長因子加速預(yù)構(gòu)擴張皮瓣成熟的研究 [J]. 中國修復(fù)重建外科雜志, 2003; 17(4): 293-297.
  26. 26. 邊杰芳, 馬中, 姚青, 等. 纖維蛋白膠釋放VEGF加速損傷動脈血管內(nèi)皮化的實驗研究 [J]. 中華普通外科雜志, 2005; 20(10): 663-665.