• 1保定市第一中心醫(yī)院腫瘤內(nèi)科（河北保定，071000）;;
  • 2河北大學(xué)中醫(yī)學(xué)院;;
  • 3中國醫(yī)學(xué)科學(xué)院 北京協(xié)和醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)研究所;;
  • 4承德市腫瘤醫(yī)院腫瘤外科;

目的觀察粒-巨噬細胞集落刺激因子（granulocyte macrophage-colony stimulating factor，GM-CSF）局部應(yīng)用于草酸鉑腹腔化療下大鼠結(jié)腸吻合口愈合過程中的組織學(xué)變化，探討其作用機制。 方法10周齡清潔級雄性Wistar大鼠60只，體重（235 ± 18） g，制備結(jié)腸吻合模型，隨機分為3組（n=20）。術(shù)后1 d，A、B組腹腔對應(yīng)注射10 mL 5%葡萄糖溶液、10 mL含草酸鉑（25 mg/kg）的5%葡萄糖溶液；C組術(shù)后即刻吻合口區(qū)域注射50 μg GM-CSF，術(shù)后1 d腹腔注射10 mL含草酸鉑（25 mg/kg）的5%葡萄糖溶液。術(shù)后觀察大鼠一般情況，于2、3、5、7 d測量吻合口破裂壓，組織學(xué)觀察并計算吻合口愈合指數(shù)，免疫組織化學(xué)染色檢測Ⅰ型膠原纖維陽性染色面積。 結(jié)果術(shù)后各組大鼠均存活至實驗完成。術(shù)后2、3 d 各組吻合口破裂壓相似（P  gt; 0.05）；5、7 d時，B組吻合口破裂壓顯著低于A、C組（P  lt; 0.05），A、C組間差異無統(tǒng)計學(xué)意義（P  gt; 0.05）。吻合口愈合指數(shù)結(jié)果示，術(shù)后各時間點，A、C組間單核細胞浸潤、黏膜上皮細胞覆蓋、黏膜下層-肌層銜接程度及肉芽組織形成相似（P  gt; 0.05），A、C組黏膜上皮細胞覆蓋及肉芽組織形成均顯著優(yōu)于B組（P  lt; 0.05）；術(shù)后2、3 d，A、C組單核細胞浸潤顯著優(yōu)于B組（P  lt; 0.05），5、7 d黏膜下層-肌層銜接程度優(yōu)于B組（P  lt; 0.05）。術(shù)后2、3 d，各組Ⅰ型膠原纖維陽性染色面積比較差異均無統(tǒng)計學(xué)意義（P  gt; 0.05）；5、7 d時A、C組Ⅰ型膠原纖維陽性染色面積顯著高于B組（P  lt; 0.05），A、C組間比較差異無統(tǒng)計學(xué)意義（P  gt; 0.05）。 結(jié)論局部注射GM-CSF可通過早期動員巨噬細胞浸潤，提高大鼠黏膜下層膠原纖維沉積，從而加速結(jié)腸愈合進程。

引用本文： 劉勇,楊陽,劉輝,宋云駿,賈喜花,張曉偉,郭建美. 粒-巨噬細胞集落刺激因子促進草酸鉑腹腔化療下大鼠結(jié)腸吻合口愈合機制的初步研究. 中國修復(fù)重建外科雜志, 2012, 26(10): 1232-1236. doi: 復(fù)制

1. Lipska MA, Bissett IP, Parry BR, et al. Anastomotic leakage after lower gastrointestinal anastomosis: men are at a higher risk. ANZ J Surg, 2006, 76(7): 579-585.
2. Mann A, Niekisch K, Schirmacher P, et al. Granulocyte-macrophage colony-stimulating factor is essential for normal wound healing. J Investig Dermatol Symp Proc, 2006, 11(1): 87-92.
3. 劉勇, 楊陽, 王娟. 早期腹腔化療與胃腸吻合口的愈合. 國際腫瘤學(xué)雜志, 2007, 34(1): 65-67.
4. 劉勇, 楊陽, 劉輝, 等. 草酸鉑腹腔化療對大鼠結(jié)腸吻合口愈合影響及粒-巨噬細胞集落刺激因子的干預(yù)效應(yīng). 中華臨床醫(yī)師雜志(電子版), 2011, 5(20): 5960-5963.
5. Verhofstad MH, Lange WP, van der Laak JA, et al. Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats. Dis Colon Rectum, 2001, 44(3): 423-431.
6. Güven A, Pehlivan M, Gökpinar I, et al. Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: light microscopic and immunohistochemical evaluation. Acta Histochem, 2007, 109(2): 122-129.
7. Hribaschek A, Pross M, Kuhn R, et al. Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin. Anticancer Drugs, 2002, 13(6): 605-614.
8. Mann A, Breuhahn K, Schirmacher P, et al. Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing: Stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol, 2001, 117(6): 1382-1390.
9. Fatouros MS, Vekinis G, Bourantas KL, et al. Influence of growth factors erythropoietin and granulocyte macrophage colony stimulating factor on mechanical strength and healing of colonic anastomoses in rats. Eur J Surg, 1999, 165(10): 986-992.
10. De Waard JW, Wobbes T, van der Linden CJ, et al. Retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses. Arch Surg, 1995, 130(9): 959-965.
11. 郝光榮. 實驗動物學(xué). 2版. 上海: 第二軍醫(yī)大學(xué)出版社, 2002: 276.
12. Dinc S, Gulcelik MA, Kuru B, et al. Effects of locally applied recombinant human granulocyte-macrophage colony-stimulating factor on ischemic bowel anastomoses in rat. Eur Surg Res, 2004, 36(1): 59-63.
13. Dinc S, Alagol H, Gulcelik MA, et al. Locally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment. World J Surg, 2002, 26(10): 1208-1213.
14. Dinc S, Ozbirecikli B, Gulcelik MA, et al. The effects of locally injected granulocyte macrophage-colony stimulating factor on the healing of intraoperatively irradiated intestinal anastomoses in rats. J Exp Clin Cancer Res, 2004, 23(1): 77-82.
15. Fang Y, Shen J, Yao M, et al. Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines. Br J Dermatol, 2010, 162(3): 478-486.
16. Miao M, Niu Y, Xie T, et al. Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation. Wound Repair Regen, 2012, 20(2): 203-213.
17. Jyung RW, Wu L, Pierce GF, et al. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery, 1994, 115(3): 325-334.
18. Witte MB, Barbul A. Repair of full-thickness bowel injury. Crit Care Med, 2003, 31(8 Suppl): S538-546.
19. Thornton FJ, Barbul A. Healing in the gastrointestinal tract. Surg Clin North Am, 1997, 77(3): 549-573.
20. Cross KJ, Mustoe TA. Growth factors in wound healing. Surg Clin North Am, 2003, 83(3): 531-545.
  1. 1. Lipska MA, Bissett IP, Parry BR, et al. Anastomotic leakage after lower gastrointestinal anastomosis: men are at a higher risk. ANZ J Surg, 2006, 76(7): 579-585.
  2. 2. Mann A, Niekisch K, Schirmacher P, et al. Granulocyte-macrophage colony-stimulating factor is essential for normal wound healing. J Investig Dermatol Symp Proc, 2006, 11(1): 87-92.
  3. 3. 劉勇, 楊陽, 王娟. 早期腹腔化療與胃腸吻合口的愈合. 國際腫瘤學(xué)雜志, 2007, 34(1): 65-67.
  4. 4. 劉勇, 楊陽, 劉輝, 等. 草酸鉑腹腔化療對大鼠結(jié)腸吻合口愈合影響及粒-巨噬細胞集落刺激因子的干預(yù)效應(yīng). 中華臨床醫(yī)師雜志(電子版), 2011, 5(20): 5960-5963.
  5. 5. Verhofstad MH, Lange WP, van der Laak JA, et al. Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats. Dis Colon Rectum, 2001, 44(3): 423-431.
  6. 6. Güven A, Pehlivan M, Gökpinar I, et al. Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: light microscopic and immunohistochemical evaluation. Acta Histochem, 2007, 109(2): 122-129.
  7. 7. Hribaschek A, Pross M, Kuhn R, et al. Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin. Anticancer Drugs, 2002, 13(6): 605-614.
  8. 8. Mann A, Breuhahn K, Schirmacher P, et al. Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing: Stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization. J Invest Dermatol, 2001, 117(6): 1382-1390.
  9. 9. Fatouros MS, Vekinis G, Bourantas KL, et al. Influence of growth factors erythropoietin and granulocyte macrophage colony stimulating factor on mechanical strength and healing of colonic anastomoses in rats. Eur J Surg, 1999, 165(10): 986-992.
  10. 10. De Waard JW, Wobbes T, van der Linden CJ, et al. Retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses. Arch Surg, 1995, 130(9): 959-965.
  11. 11. 郝光榮. 實驗動物學(xué). 2版. 上海: 第二軍醫(yī)大學(xué)出版社, 2002: 276.
  12. 12. Dinc S, Gulcelik MA, Kuru B, et al. Effects of locally applied recombinant human granulocyte-macrophage colony-stimulating factor on ischemic bowel anastomoses in rat. Eur Surg Res, 2004, 36(1): 59-63.
  13. 13. Dinc S, Alagol H, Gulcelik MA, et al. Locally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment. World J Surg, 2002, 26(10): 1208-1213.
  14. 14. Dinc S, Ozbirecikli B, Gulcelik MA, et al. The effects of locally injected granulocyte macrophage-colony stimulating factor on the healing of intraoperatively irradiated intestinal anastomoses in rats. J Exp Clin Cancer Res, 2004, 23(1): 77-82.
  15. 15. Fang Y, Shen J, Yao M, et al. Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines. Br J Dermatol, 2010, 162(3): 478-486.
  16. 16. Miao M, Niu Y, Xie T, et al. Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation. Wound Repair Regen, 2012, 20(2): 203-213.
  17. 17. Jyung RW, Wu L, Pierce GF, et al. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery, 1994, 115(3): 325-334.
  18. 18. Witte MB, Barbul A. Repair of full-thickness bowel injury. Crit Care Med, 2003, 31(8 Suppl): S538-546.
  19. 19. Thornton FJ, Barbul A. Healing in the gastrointestinal tract. Surg Clin North Am, 1997, 77(3): 549-573.
  20. 20. Cross KJ, Mustoe TA. Growth factors in wound healing. Surg Clin North Am, 2003, 83(3): 531-545.