• 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(zhǎng)因子(VEGF)促進(jìn)腸吻合口愈合的有效性。方法 通過(guò)在兔盲腸穿孔建立腹腔感染的動(dòng)物模型,12 h后行腸切除及腸吻合。動(dòng)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(jì)各組吻合口漏發(fā)生情況,測(cè)量未發(fā)生吻合口漏的動(dòng)物的吻合口破裂壓,檢測(cè)吻合口組織羥脯氨酸含量及VEGF表達(dá)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(duì)照組,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P gt;0.05),而VEGF+生物蛋白膠組則明顯低于對(duì)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(dá)陽(yáng)性細(xì)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(jìn)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(zhǎng)因子促進(jìn)腸吻合口愈合的研究. 中國(guó)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(zhǎng)激素促進(jìn)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(jī)對(duì)照研究 [J]. 中華胃腸外科雜志, 2005; 8(1): 43-45.
6. 李幼生, 鮑揚(yáng), 江濤, 等. 生長(zhǎng)激素、纖維蛋白膠促進(jìn)腹腔感染大鼠腸吻合口愈合的動(dòng)態(tài)研究 [J]. 腸外與腸內(nèi)營(yíng)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(zhǎng)因子與腫瘤血管生成 [J]. 中國(guó)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(zhǎng)因子治療急性肢體缺血的研究 [J]. 中國(guó)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(guò)程中血管內(nèi)皮生長(zhǎng)因子及β3整合素的表達(dá) [J]. 中國(guó)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(dòng)力學(xué)研究 [J]. 西北國(guó)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(xì)胞生長(zhǎng)因子和堿性成纖維細(xì)胞生長(zhǎng)因子加速預(yù)構(gòu)擴(kuò)張皮瓣成熟的研究 [J]. 中國(guó)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(dòng)脈血管內(nèi)皮化的實(shí)驗(yàn)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(zhǎng)激素促進(jìn)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(jī)對(duì)照研究 [J]. 中華胃腸外科雜志, 2005; 8(1): 43-45.
  6. 6. 李幼生, 鮑揚(yáng), 江濤, 等. 生長(zhǎng)激素、纖維蛋白膠促進(jìn)腹腔感染大鼠腸吻合口愈合的動(dòng)態(tài)研究 [J]. 腸外與腸內(nèi)營(yíng)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(zhǎng)因子與腫瘤血管生成 [J]. 中國(guó)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(zhǎng)因子治療急性肢體缺血的研究 [J]. 中國(guó)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(guò)程中血管內(nèi)皮生長(zhǎng)因子及β3整合素的表達(dá) [J]. 中國(guó)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(dòng)力學(xué)研究 [J]. 西北國(guó)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(xì)胞生長(zhǎng)因子和堿性成纖維細(xì)胞生長(zhǎng)因子加速預(yù)構(gòu)擴(kuò)張皮瓣成熟的研究 [J]. 中國(guó)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(dòng)脈血管內(nèi)皮化的實(shí)驗(yàn)研究 [J]. 中華普通外科雜志, 2005; 20(10): 663-665.