• 四川大學華西醫(yī)院胃腸外科中心（成都 610041）;

目的  探討短期應用生長激素對胃腸外科手術后患者血清胰島素樣生長因子-1（IGF-1）水平和營養(yǎng)狀況的影響，并評價其對于惡性腫瘤復發(fā)的危險性。方法  48例接受胃腸道中等以上手術的患者，隨機分為研究組（n=24）和對照組（n=24）。2組患者的基線情況一致，具有可比性（P gt;0.05）。2組患者術后治療和營養(yǎng)支持方案相同，研究組于術后第3天開始每日給予重組人生長激素（0.15 U/kg），對照組給予安慰劑，連續(xù)7 d。術后3～9 d，測定每日氮平衡； 檢測術前1 d、術后3 d和10 d的血清白蛋白、纖維連接蛋白和IGF-1水平； 觀察患者術后并發(fā)癥和不良反應發(fā)生情況； 惡性腫瘤患者隨訪2年。 結果  研究組累積氮平衡明顯高于對照組〔（11.37±16.82） g比（－9.11±17.52） g，P＜0.01〕。生長激素治療結束后（術后第10天），2組患者間血清白蛋白、纖維連接蛋白和IGF-1水平比較差異無統(tǒng)計學意義（P gt;0.05）； 但與術后第3天相比，研究組血清纖維連接蛋白水平回升幅度明顯大于對照組〔(22.8±5.8) mg/L比（9.6±3.6） mg/L，P＜0.05〕。生長激素治療期間未出現(xiàn)嚴重不良反應及并發(fā)癥。隨訪期間2組惡性腫瘤患者的腫瘤復發(fā)率差異無統(tǒng)計學意義（P gt;0.05）。 結論  短期小劑量生長激素聯(lián)合早期營養(yǎng)支持能促進胃腸外科手術后患者的氮平衡和蛋白代謝，且不會促進腫瘤的復發(fā)； 但對血清IGF-1水平無明顯影響。

引用本文： 張明鳴,周勇,伍曉汀. 生長激素短期應用對胃腸外科手術后患者營養(yǎng)狀況和血清IGF-1的影響. 中國普外基礎與臨床雜志, 2009, 16(12): 968-973. doi: 復制

1. Kreymann KG. Early nutrition support in critical care: a European perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 156-159.
2. Scurlock C, Mechanick JI. Early nutrition support in the intensive care unit: a US perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 152-155.
3. 羅世成, 郭建輝, 朱軍, 等. 胃腸道腫瘤患者術后早期腸內(nèi)營養(yǎng)與腸外營養(yǎng)支持的隨機對照研究 [Ｊ]. 中國普外基礎與臨床雜志, 2007; 14(3): 324-328.
4. Kudsk KA. Immunonutrition in surgery and critical care [Ｊ]. Annu Rev Nutr, 2006; 26: 463-479.
5. 張明鳴, 伍曉汀. 腸康復治療和短腸綜合征 [Ｊ]. 中國普外基礎與臨床雜志, 2007; 14(1): 117-119.
6. 陳先鋒, 劉作金, 李旭宏, 等. TPN聯(lián)合生長激素對胃腸道惡性腫瘤患者術后應激反應的抑制作用 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(1): 45-47.
7. Akaza H, Matsuki K, Matsushima H, et al. Stimulatory effects of growth hormone on rat bladder carcinogenesis [Ｊ]. Cancer, 1991; 68(11): 2418-2421.
8. Maneatis T, Baptista J, Connelly K, et al. Growth hormone safety update from the National Cooperative Growth Study [Ｊ]. J Pediatr Endocrinol Metab, 2000; 13 Suppl 2: 1035-1044.
9. Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [Ｊ]. JPEN J Parenter Enteral Nutr, 2000; 24(3): 140-144.
10. Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-Ⅰ, and insulin-like growth factor binding proteins in the catabolic response to injury and infection [Ｊ]. Curr Opin Clin Nutr Metab Care, 2002; 5(3): 271-279.
11. Mller N, Jrgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects [Ｊ]. Endocr Rev, 2009; 30(2): 152-177.
12. Luo SM, Liang LJ, Lai JM. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis [Ｊ]. World J Gastroenterol, 2004; 10(9): 1292-1296.
13. Duska F, Fric M, Waldauf P, et al. Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation [Ｊ]. Crit Care Med, 2008; 36(6): 1707-1713.
14. Hammarqvist F, Sandgren A, Andersson K, et al. Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma [Ｊ]. Surgery, 2001; 129(5): 576-586.
15. Jensen MB, Kissmeyer-Nielsen P, Laurberg S. Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass [Ｊ]. Am J Clin Nutr, 1998; 68(4): 840-846.
16. Jones CH, Newstead CG, Will EJ, et al. Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure [Ｊ]. Nephrol Dial Transplant, 1997; 12(7): 1406-1413.
17. Akenami FO, Koskiniemi M, Siimes MA, et al. Assessment of plasma fibronectin in malnourished Nigerian children [Ｊ]. J Pediatr Gastroenterol Nutr, 1997; 24(2): 183-188.
18. Heemskerk VH, Daemen MA, Buurman WA. Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation [Ｊ]. Cytokine Growth Factor Rev, 1999; 10(1): 5-14.
19. Berneis K, Keller U. Metabolic actions of growth hormone: direct and indirect [Ｊ]. Baillieres Clin Endocrinol Metab, 1996; 10(3): 337-352.
20. LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1 [Ｊ]. Nat Clin Pract Endocrinol Metab, 2007; 3(3): 302-310.
21. Hayes VY, Urban RJ, Jiang J, et al. Recombinant human growth hormone and recombinant human insulin-like growth factor Ⅰ diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects [Ｊ]. J Clin Endocrinol Metab, 2001; 86(5): 2211-2219.
22. Mauras N, Haymond MW. Are the metabolic effects of GH and IGF-Ⅰ separable ? [Ｊ]. Growth Horm IGF Res, 2005; 15(1): 19-27.
23. Mauras N, Martinez V, Rini A, et al. Recombinant human insulin-like growth factor Ⅰ has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism [Ｊ]. J Clin Endocrinol Metab, 2000; 85(9): 3036-3042.
24. Shimoda N, Tashiro T, Yamamori H, et al. Effects of gr-owth hormone and insulin-like growth factor-1 on protein metabolism, gut morphology, and cell-mediated immunity in burned rats [Ｊ]. Nutrition, 1997; 13(6): 540-516.
25. Nakhjavani M, Esteghamati A, Hamidi S, et al. Changes in growth hormone and insulin-like growth factor-Ⅰ levels in the acute stage after open heart surgery and at the time of discharge [Ｊ]. Exp Clin Endocrinol Diabetes, 2009; 117(8): 413-416.
26. Cao J, Luo SM, Liang L, et al. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis [Ｊ]. JPEN J Parenter Enteral Nutr, 2007; 31(6): 496-501.
27. Inaba T, Saito H, Fukushima R, et al. Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury [Ｊ]. JPEN J Parenter Enteral Nutr, 1997; 21(2): 55-62.
28. Sevette A, Smith RC, Aslani A, et al. Does growth hormone allow more efficient nitrogen sparing in postoperative patients requiring parenteral nutrition? A double-blind, placebo-controlled randomised trial [Ｊ]. Clin Nutr, 2005; 24(6): 943-955.
29. Sánchez-Gómez M, Malmlf K, Mejía W, et al. Insulin-like growth factor-Ⅰ, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat [Ｊ]. Br J Nutr, 1999; 81(2): 145-152.
30. Tacke J, Bolder U, Lhlein D. Improved cumulated nitrogen balance after administration of recombinant human growth hormone in patients undergoing gastrointestinal surgery [Ｊ]. Infusionsther Transfusionsmed, 1994; 21(1): 24-29.
31. Ng EH, Rock CS, Lazarus D, et al. Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model [Ｊ]. J Surg Res, 1991; 51(2): 99-105.
32. Wolf RF, Ng B, Weksler B, Burt M, et al. Effect of growth hormone on tumor and host in an animal model [Ｊ]. Ann Surg Oncol, 1994; 1(4): 314-320.
33. Torosian MH. Growth hormone and prostate cancer growth and metastasis in tumor-bearing animals [Ｊ]. J Pediatr Endocrinol, 1993; 6(1): 93-97.
34. Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and somatostatin therapy of cancer cachexia [Ｊ]. Cancer, 1994; 73(5): 1499-1504.
35. van Buul-Offers SC, Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system [Ｊ]. Cell Mol Life Sci, 1998; 54(10): 1083-1094.
  1. 1. Kreymann KG. Early nutrition support in critical care: a European perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 156-159.
  2. 2. Scurlock C, Mechanick JI. Early nutrition support in the intensive care unit: a US perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 152-155.
  3. 3. 羅世成, 郭建輝, 朱軍, 等. 胃腸道腫瘤患者術后早期腸內(nèi)營養(yǎng)與腸外營養(yǎng)支持的隨機對照研究 [Ｊ]. 中國普外基礎與臨床雜志, 2007; 14(3): 324-328.
  4. 4. Kudsk KA. Immunonutrition in surgery and critical care [Ｊ]. Annu Rev Nutr, 2006; 26: 463-479.
  5. 5. 張明鳴, 伍曉汀. 腸康復治療和短腸綜合征 [Ｊ]. 中國普外基礎與臨床雜志, 2007; 14(1): 117-119.
  6. 6. 陳先鋒, 劉作金, 李旭宏, 等. TPN聯(lián)合生長激素對胃腸道惡性腫瘤患者術后應激反應的抑制作用 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(1): 45-47.
  7. 7. Akaza H, Matsuki K, Matsushima H, et al. Stimulatory effects of growth hormone on rat bladder carcinogenesis [Ｊ]. Cancer, 1991; 68(11): 2418-2421.
  8. 8. Maneatis T, Baptista J, Connelly K, et al. Growth hormone safety update from the National Cooperative Growth Study [Ｊ]. J Pediatr Endocrinol Metab, 2000; 13 Suppl 2: 1035-1044.
  9. 9. Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [Ｊ]. JPEN J Parenter Enteral Nutr, 2000; 24(3): 140-144.
  10. 10. Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-Ⅰ, and insulin-like growth factor binding proteins in the catabolic response to injury and infection [Ｊ]. Curr Opin Clin Nutr Metab Care, 2002; 5(3): 271-279.
  11. 11. Mller N, Jrgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects [Ｊ]. Endocr Rev, 2009; 30(2): 152-177.
  12. 12. Luo SM, Liang LJ, Lai JM. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis [Ｊ]. World J Gastroenterol, 2004; 10(9): 1292-1296.
  13. 13. Duska F, Fric M, Waldauf P, et al. Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation [Ｊ]. Crit Care Med, 2008; 36(6): 1707-1713.
  14. 14. Hammarqvist F, Sandgren A, Andersson K, et al. Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma [Ｊ]. Surgery, 2001; 129(5): 576-586.
  15. 15. Jensen MB, Kissmeyer-Nielsen P, Laurberg S. Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass [Ｊ]. Am J Clin Nutr, 1998; 68(4): 840-846.
  16. 16. Jones CH, Newstead CG, Will EJ, et al. Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure [Ｊ]. Nephrol Dial Transplant, 1997; 12(7): 1406-1413.
  17. 17. Akenami FO, Koskiniemi M, Siimes MA, et al. Assessment of plasma fibronectin in malnourished Nigerian children [Ｊ]. J Pediatr Gastroenterol Nutr, 1997; 24(2): 183-188.
  18. 18. Heemskerk VH, Daemen MA, Buurman WA. Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation [Ｊ]. Cytokine Growth Factor Rev, 1999; 10(1): 5-14.
  19. 19. Berneis K, Keller U. Metabolic actions of growth hormone: direct and indirect [Ｊ]. Baillieres Clin Endocrinol Metab, 1996; 10(3): 337-352.
  20. 20. LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1 [Ｊ]. Nat Clin Pract Endocrinol Metab, 2007; 3(3): 302-310.
  21. 21. Hayes VY, Urban RJ, Jiang J, et al. Recombinant human growth hormone and recombinant human insulin-like growth factor Ⅰ diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects [Ｊ]. J Clin Endocrinol Metab, 2001; 86(5): 2211-2219.
  22. 22. Mauras N, Haymond MW. Are the metabolic effects of GH and IGF-Ⅰ separable ? [Ｊ]. Growth Horm IGF Res, 2005; 15(1): 19-27.
  23. 23. Mauras N, Martinez V, Rini A, et al. Recombinant human insulin-like growth factor Ⅰ has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism [Ｊ]. J Clin Endocrinol Metab, 2000; 85(9): 3036-3042.
  24. 24. Shimoda N, Tashiro T, Yamamori H, et al. Effects of gr-owth hormone and insulin-like growth factor-1 on protein metabolism, gut morphology, and cell-mediated immunity in burned rats [Ｊ]. Nutrition, 1997; 13(6): 540-516.
  25. 25. Nakhjavani M, Esteghamati A, Hamidi S, et al. Changes in growth hormone and insulin-like growth factor-Ⅰ levels in the acute stage after open heart surgery and at the time of discharge [Ｊ]. Exp Clin Endocrinol Diabetes, 2009; 117(8): 413-416.
  26. 26. Cao J, Luo SM, Liang L, et al. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis [Ｊ]. JPEN J Parenter Enteral Nutr, 2007; 31(6): 496-501.
  27. 27. Inaba T, Saito H, Fukushima R, et al. Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury [Ｊ]. JPEN J Parenter Enteral Nutr, 1997; 21(2): 55-62.
  28. 28. Sevette A, Smith RC, Aslani A, et al. Does growth hormone allow more efficient nitrogen sparing in postoperative patients requiring parenteral nutrition? A double-blind, placebo-controlled randomised trial [Ｊ]. Clin Nutr, 2005; 24(6): 943-955.
  29. 29. Sánchez-Gómez M, Malmlf K, Mejía W, et al. Insulin-like growth factor-Ⅰ, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat [Ｊ]. Br J Nutr, 1999; 81(2): 145-152.
  30. 30. Tacke J, Bolder U, Lhlein D. Improved cumulated nitrogen balance after administration of recombinant human growth hormone in patients undergoing gastrointestinal surgery [Ｊ]. Infusionsther Transfusionsmed, 1994; 21(1): 24-29.
  31. 31. Ng EH, Rock CS, Lazarus D, et al. Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model [Ｊ]. J Surg Res, 1991; 51(2): 99-105.
  32. 32. Wolf RF, Ng B, Weksler B, Burt M, et al. Effect of growth hormone on tumor and host in an animal model [Ｊ]. Ann Surg Oncol, 1994; 1(4): 314-320.
  33. 33. Torosian MH. Growth hormone and prostate cancer growth and metastasis in tumor-bearing animals [Ｊ]. J Pediatr Endocrinol, 1993; 6(1): 93-97.
  34. 34. Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and somatostatin therapy of cancer cachexia [Ｊ]. Cancer, 1994; 73(5): 1499-1504.
  35. 35. van Buul-Offers SC, Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system [Ｊ]. Cell Mol Life Sci, 1998; 54(10): 1083-1094.