• 四川大學(xué)華西醫(yī)院胃腸外科中心（成都 610041）;

目的  探討短期應(yīng)用生長激素對胃腸外科手術(shù)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(fù)發(fā)的危險性。方法  48例接受胃腸道中等以上手術(shù)的患者，隨機(jī)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(shù)后治療和營養(yǎng)支持方案相同，研究組于術(shù)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(shù)后3～9 d，測定每日氮平衡； 檢測術(shù)前1 d、術(shù)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(shù)后并發(fā)癥和不良反應(yīng)發(fā)生情況； 惡性腫瘤患者隨訪2年。 結(jié)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(jié)束后（術(shù)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(xué)意義（P gt;0.05）； 但與術(shù)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(yán)重不良反應(yīng)及并發(fā)癥。隨訪期間2組惡性腫瘤患者的腫瘤復(fù)發(fā)率差異無統(tǒng)計學(xué)意義（P gt;0.05）。 結(jié)論  短期小劑量生長激素聯(lián)合早期營養(yǎng)支持能促進(jìn)胃腸外科手術(shù)后患者的氮平衡和蛋白代謝，且不會促進(jìn)腫瘤的復(fù)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(yīng)用對胃腸外科手術(shù)后患者營養(yǎng)狀況和血清IGF-1的影響. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(12): 968-973. doi: 復(fù)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(shù)后早期腸內(nèi)營養(yǎng)與腸外營養(yǎng)支持的隨機(jī)對照研究 [Ｊ]. 中國普外基礎(chǔ)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(fù)治療和短腸綜合征 [Ｊ]. 中國普外基礎(chǔ)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(shù)后應(yīng)激反應(yīng)的抑制作用 [Ｊ]. 中國普外基礎(chǔ)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(shù)后早期腸內(nèi)營養(yǎng)與腸外營養(yǎng)支持的隨機(jī)對照研究 [Ｊ]. 中國普外基礎(chǔ)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(fù)治療和短腸綜合征 [Ｊ]. 中國普外基礎(chǔ)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(shù)后應(yīng)激反應(yīng)的抑制作用 [Ｊ]. 中國普外基礎(chǔ)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.