Protective Effects of Recombinant Human Growth Hormone on Intestinal Barrier Function_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Wei , WANG Xinbo , TONG Zhongxun , WANG Zhikang , LI Li

The First Department of Hepatobiliaropancreatic Surgery,The Affiliated Ganmei Hospital of Kunming Medical College and The First People’s Hospital of Kunming City, Kunming 650011, China;

Corresponding author：

Keywords：

Recombinant human growth hormone; Intestinal barrier function; Mechanism; Apoptosis

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Objective To investigate the protective effects and the mechanism of recombinant human growth hormone on the intestinal barrier function. Methods The literatures of recent years were reviewed and summarized． Results The recombinant human growth hormone not only prevent mucosal cells and immunological cells from apoptosis, but also antagonize the damage of NO, cytokines, as well as endotoxin on intestinal barrier. What’s more, it increases the intestinal uptake and utilization of glutamine. All of the above could maintain the integrity and functions of the intestinal barrier. Conclusion The recombinant human growth hormone protects the intestinal barrier function through different ways.

Citation： LIU Wei,WANG Xinbo,TONG Zhongxun,WANG Zhikang,LI Li. Protective Effects of Recombinant Human Growth Hormone on Intestinal Barrier Function. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(11): 948-951. doi: Copy

1.	Smith JR, Benghuzzi H, Tucci M, et al．The effects of growth hormone and insulin-like growth factor on the proliferation rate and morphology of RAW 264.7 macrophages [J]. Biomed Sci Instrum, 2000; 36: 111-116.
2.	Waters MJ, Hoang HN, Fairlie DP, et al. New insights into growth hormone action [J]． J Mol Endocrinol, 2006; 36(1): 1-7.
3.	Redelman D, Welniak LA, Taub D, et al. Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network [J]．Cell Immunol, 2008; 252(1-2): 111-121.
4.	石毅，赵玉沛，廖泉, 等. 生长激素对胰腺癌移植瘤细胞周期及宿主IGF-1与小肠黏膜形态的影响 [J]. 中国实用外科杂志, 2007; 27(10): 829-833.
5.	宋国栋, 王德昌, 贾军, 等. 重组人生长激素对烧伤大鼠肠粘膜结构及细胞凋亡的影响 [J]. 中华烧伤杂志， 2002； 18(4): 207-209.
6.	秦爽, 贺育兰, 杨静，等. 重组人生长激素对内毒素诱导人巨噬细胞产生TNF-α、IL-1β含量的影响 [J]. 中国感染控制杂志, 2008； 7(1)： 9-11.
7.	郭光华，蔡晨，李国辉. 肠内免疫营养联合重组人生长激素对烫伤大鼠的治疗作用 [J]. 中国危重病急救医学, 2006； 18(1)： 42-45.
8.	王兴鹏，王冰娴，吴建新，等. 生长激素对实验性急性坏死性胰腺炎肠道细菌移居的影响 [J]. 中华消化杂志, 2000； 20(3)： 171-174.
9.	Scopa CD, Koureleas S, Tsamandas AC, et al. Beneficial effects of growth hormone and insulin-like growth factor Ⅰ on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats [J]. J Am Coll Surg, 2000; 190(4): 423-431.
10.	Yang ZW, Li JG, Mao XG, et al, Effects of recombinant human growth hormone on intestinal translocation of bacteria and endotoxin in rats with obstructive jaundice [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(3): 445-449.
11.	黄英，王树人，应明英, 等. 重组人生长激素对败血症大鼠的实验治疗 [J]. 中国病理生理杂志, 2003; 19(9)： 1253-1256.
12.	周彤, 伍晓汀, 罗婷, 等. 生长激素对脂多糖刺激大鼠腹腔巨噬细胞NO产生及iNOS mRNA表达的影响及意义 [J]. 华西医学, 2006； 21(3): 535-537.
13.	徐一洲, 黄煌, 曹玥, 等. 重组人生长激素对败血症大鼠炎症调控网络的影响 [J]. 华西药学杂志, 2007; 22(2)： 142-144.
14.	Berni Canani R, Cirillo P, Mallardo G, et al . Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway [J]. World J Gastroenterol, 2006; 12(29): 4710-4715.
15.	Lobie PE, Breipohl W, Waters MJ. Growth hormone receptor expression in the rat gastrointestinal tract [J]. Endocrinology, 1990; 126(1): 299-306.
16.	Jeay S, Sonenshein GE, Postel-Vinay MC, et al. Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: new insights into signaling pathways [J]. Mol Cell Endocrinol, 2002; 188(1-2): 1-7.
17.	马少林, 王晓红, 杨晓军, 等. 创伤-失血性休克与细胞免疫功能的临床研究 [J]. 宁夏医学杂志, 2007; 29(7): 605-606.
18.	于勇, 盛志勇, 田惠民, 等. 大鼠烫伤后肠道免疫屏障损伤的实验研究 [J]. 中华整形烧伤外科杂志, 1996; 12(2): 86-89.
19.	刘海波, 孙少川, 郑春宁, 等. 重组人生长激素对肠缺血再灌注大鼠肠壁IgA浆细胞凋亡及P53基因表达影响的实验研究 [J]. 中国现代普通外科进展, 2006； 9(6)： 337-339.
20.	孙少川, 郑春宁, 刘国勤，等. 重组人生长激素对大鼠肠道缺血再灌注后肠壁组织T淋巴细胞亚群和浆细胞凋亡的影响 [J]. 中华实验外科杂志, 2006; 23(5): 605-606.
21.	Hiroki Mitsunakaa, Hiroaki Dobashia, Makoto Satoa.Gr-owth Hormone prevents fas-Induced apoptosis in lymphocytes through modulation of Bcl-2 and Caspase-3 [J]. Neuroimmunomodulation, 2001; 9（5）: 256-262.
22.	王辉, 邓洁英, 史轶蘩. 生长激素调节T淋巴细胞的功能 [J]. 中国免疫学杂志, 2000; 16(9): 480-484.
23.	Matarese LE, Abu-Elmagd K. Can growth hormone and glutamine reduce parenteral nutrition requirements in patients with short-bowel syndrome? [J]．Nat Clin Pract Gastroenterol Hepatol, 2006; 3(4): 194-195.
24.	Shulman DI. Gastrointestinal effects of growth hormone [J]. Endocrine, 2000; 12(2): 147-152.
25.	Byrne TA, Wilmore DW, Iyer K. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial [J]. Ann Surg, 2005; 242(5): 655-661.
26.	Ray EC, Avissar NE, Salloum R, et al. Growth hormone and epidermal growth factor upregulate specific sodium-dependent glutamine uptake systems in human intestinal C2BBe1 cells [J]. J Nutr, 2005; 135(1): 14-18.
27.	Jeay S, Sonenshein GE, Kelly PA, et al. Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase [J]. Endocrinology, 2001; 142(1): 147-156.
28.	Jeay S, Sonenshein GE, Postel-Vinay MC, et al. Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line [J]. Mol Endocrinol, 2000; 14(5): 650-661.
29.	Darmaun D, Hayes V, Schaeffer D, et al. Effects of glutamine and recombinant human growth hormone on protein metabolism in prepubertal children with cystic fibrosis [J]. J Clin Endocrinol Metab, 2004; 89(3): 1146-1152.
30.	Bogazzi F, Russo D, Locci MT. Apoptosis is reduced in the colonic mucosa of patients with acromegaly [J]. Clin Endocrinol (Oxf), 2005; 63(6): 683-688.
31.	Baixeras E, Jeay S, Kelly PA, et al. The proliferative and antiapoptotic actions of growth hormone and insulin-like growth factor-1 are mediated through distinct signaling pathways in the Pro-B Ba/F3 cell line [J]. Endocrinology, 2001; 142(7): 2968-2977.
32.	Jeschke MG, Herndon DN, Finnerty CC, et al. The effect of growth hormone on gut mucosal homeostasis and cellular mediators after severe trauma [J]. J Surg Res, 2005; 127(2): 183-189.
33.	宋军, 刘金钢, 王勇, 等. 生长激素对实验性梗阻性黄疸时肿瘤坏死因子α的影响 [J]. 中国医师杂志, 2006; 8(12): 1596-1597.
34.	刘敏丰, 高志光, 秦环龙. 生长激素和谷氨酰胺对脓毒症大鼠细胞因子和氨基酸代谢的影响 [J]. 中国普外基础与临床杂志, 2006; 13(5): 535-539.
35.	梁志刚, 刘锡麟, 李江, 等. 重组人生长激素对重度烧伤后细胞因子的影响 [J]. 中华烧伤杂志, 2002; 18(1): 49-51.
36.	Sodhi A, Tripathi A. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB [J]. Cytokine, 2008; 41(2): 162-173.
37.	潘云萍, 钟湧, 李建华, 等. 严重创伤后肠黏膜屏障损伤及生长激素治疗作用的临床研究 [J]. 中国危重病急救医学, 2007; 19(8): 496.
38.	黄鹏, 熊炯炘, 王春友, 等. 生长激素和生长抑素联合应用对重症急性胰腺炎患者肠黏膜屏障保护作用的研究 [J]. 临床外科杂志, 2007; 15(3): 178-180.
39.	刘波, 邓宇, 许瑞云. 谷氨酰胺与重组人生长激素对肝硬化患者肠黏膜屏障的影响 [J]. 医学临床研究, 2006; 23(10): 1598-1600.
40.	汤照峰，凌云彪，郝峥, 等. Gln和rhGH对门脉高压症术后肠粘膜屏障及增殖细胞核抗原表达的影响 [J]. 中国病理生理杂志, 2006; 22(9)： 1825-1828.
41.	佟大年，杨俊，秦环龙. 生长激素及谷氨酰胺强化的肠外营养治疗对外科重症患者机体组成及肠屏障功能的影响 [J]. 中国临床营养杂志, 2006; 14(5)： 289-295.
42.	王大庆, 陈静, 万勇. 乌司他丁和生长激素联合应用改善严重腹腔感染合并呼吸循环功能障碍患者的疗效观察 [J]. 中国普外基础与临床杂志, 2008; 15(4): 283-284.
43.	Takala J, Ruokonen E, Webster NR， et al． Increased mortality associated with growth hormone treatment in critically ill adults [J]． N Engl J Med, 1999; 341(11): 785-792.
44.	周建平，刘祺. 生长激素对人结肠癌细胞作用的研究 [J]. 中国普外基础与临床杂志, 2005; 12(4): 390-392.

1. Smith JR, Benghuzzi H, Tucci M, et al．The effects of growth hormone and insulin-like growth factor on the proliferation rate and morphology of RAW 264.7 macrophages [J]. Biomed Sci Instrum, 2000; 36: 111-116.
2. Waters MJ, Hoang HN, Fairlie DP, et al. New insights into growth hormone action [J]． J Mol Endocrinol, 2006; 36(1): 1-7.
3. Redelman D, Welniak LA, Taub D, et al. Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network [J]．Cell Immunol, 2008; 252(1-2): 111-121.
4. 石毅，赵玉沛，廖泉, 等. 生长激素对胰腺癌移植瘤细胞周期及宿主IGF-1与小肠黏膜形态的影响 [J]. 中国实用外科杂志, 2007; 27(10): 829-833.
5. 宋国栋, 王德昌, 贾军, 等. 重组人生长激素对烧伤大鼠肠粘膜结构及细胞凋亡的影响 [J]. 中华烧伤杂志， 2002； 18(4): 207-209.
6. 秦爽, 贺育兰, 杨静，等. 重组人生长激素对内毒素诱导人巨噬细胞产生TNF-α、IL-1β含量的影响 [J]. 中国感染控制杂志, 2008； 7(1)： 9-11.
7. 郭光华，蔡晨，李国辉. 肠内免疫营养联合重组人生长激素对烫伤大鼠的治疗作用 [J]. 中国危重病急救医学, 2006； 18(1)： 42-45.
8. 王兴鹏，王冰娴，吴建新，等. 生长激素对实验性急性坏死性胰腺炎肠道细菌移居的影响 [J]. 中华消化杂志, 2000； 20(3)： 171-174.
9. Scopa CD, Koureleas S, Tsamandas AC, et al. Beneficial effects of growth hormone and insulin-like growth factor Ⅰ on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats [J]. J Am Coll Surg, 2000; 190(4): 423-431.
10. Yang ZW, Li JG, Mao XG, et al, Effects of recombinant human growth hormone on intestinal translocation of bacteria and endotoxin in rats with obstructive jaundice [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(3): 445-449.
11. 黄英，王树人，应明英, 等. 重组人生长激素对败血症大鼠的实验治疗 [J]. 中国病理生理杂志, 2003; 19(9)： 1253-1256.
12. 周彤, 伍晓汀, 罗婷, 等. 生长激素对脂多糖刺激大鼠腹腔巨噬细胞NO产生及iNOS mRNA表达的影响及意义 [J]. 华西医学, 2006； 21(3): 535-537.
13. 徐一洲, 黄煌, 曹玥, 等. 重组人生长激素对败血症大鼠炎症调控网络的影响 [J]. 华西药学杂志, 2007; 22(2)： 142-144.
14. Berni Canani R, Cirillo P, Mallardo G, et al . Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway [J]. World J Gastroenterol, 2006; 12(29): 4710-4715.
15. Lobie PE, Breipohl W, Waters MJ. Growth hormone receptor expression in the rat gastrointestinal tract [J]. Endocrinology, 1990; 126(1): 299-306.
16. Jeay S, Sonenshein GE, Postel-Vinay MC, et al. Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: new insights into signaling pathways [J]. Mol Cell Endocrinol, 2002; 188(1-2): 1-7.
17. 马少林, 王晓红, 杨晓军, 等. 创伤-失血性休克与细胞免疫功能的临床研究 [J]. 宁夏医学杂志, 2007; 29(7): 605-606.
18. 于勇, 盛志勇, 田惠民, 等. 大鼠烫伤后肠道免疫屏障损伤的实验研究 [J]. 中华整形烧伤外科杂志, 1996; 12(2): 86-89.
19. 刘海波, 孙少川, 郑春宁, 等. 重组人生长激素对肠缺血再灌注大鼠肠壁IgA浆细胞凋亡及P53基因表达影响的实验研究 [J]. 中国现代普通外科进展, 2006； 9(6)： 337-339.
20. 孙少川, 郑春宁, 刘国勤，等. 重组人生长激素对大鼠肠道缺血再灌注后肠壁组织T淋巴细胞亚群和浆细胞凋亡的影响 [J]. 中华实验外科杂志, 2006; 23(5): 605-606.
21. Hiroki Mitsunakaa, Hiroaki Dobashia, Makoto Satoa.Gr-owth Hormone prevents fas-Induced apoptosis in lymphocytes through modulation of Bcl-2 and Caspase-3 [J]. Neuroimmunomodulation, 2001; 9（5）: 256-262.
22. 王辉, 邓洁英, 史轶蘩. 生长激素调节T淋巴细胞的功能 [J]. 中国免疫学杂志, 2000; 16(9): 480-484.
23. Matarese LE, Abu-Elmagd K. Can growth hormone and glutamine reduce parenteral nutrition requirements in patients with short-bowel syndrome? [J]．Nat Clin Pract Gastroenterol Hepatol, 2006; 3(4): 194-195.
24. Shulman DI. Gastrointestinal effects of growth hormone [J]. Endocrine, 2000; 12(2): 147-152.
25. Byrne TA, Wilmore DW, Iyer K. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial [J]. Ann Surg, 2005; 242(5): 655-661.
26. Ray EC, Avissar NE, Salloum R, et al. Growth hormone and epidermal growth factor upregulate specific sodium-dependent glutamine uptake systems in human intestinal C2BBe1 cells [J]. J Nutr, 2005; 135(1): 14-18.
27. Jeay S, Sonenshein GE, Kelly PA, et al. Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase [J]. Endocrinology, 2001; 142(1): 147-156.
28. Jeay S, Sonenshein GE, Postel-Vinay MC, et al. Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line [J]. Mol Endocrinol, 2000; 14(5): 650-661.
29. Darmaun D, Hayes V, Schaeffer D, et al. Effects of glutamine and recombinant human growth hormone on protein metabolism in prepubertal children with cystic fibrosis [J]. J Clin Endocrinol Metab, 2004; 89(3): 1146-1152.
30. Bogazzi F, Russo D, Locci MT. Apoptosis is reduced in the colonic mucosa of patients with acromegaly [J]. Clin Endocrinol (Oxf), 2005; 63(6): 683-688.
31. Baixeras E, Jeay S, Kelly PA, et al. The proliferative and antiapoptotic actions of growth hormone and insulin-like growth factor-1 are mediated through distinct signaling pathways in the Pro-B Ba/F3 cell line [J]. Endocrinology, 2001; 142(7): 2968-2977.
32. Jeschke MG, Herndon DN, Finnerty CC, et al. The effect of growth hormone on gut mucosal homeostasis and cellular mediators after severe trauma [J]. J Surg Res, 2005; 127(2): 183-189.
33. 宋军, 刘金钢, 王勇, 等. 生长激素对实验性梗阻性黄疸时肿瘤坏死因子α的影响 [J]. 中国医师杂志, 2006; 8(12): 1596-1597.
34. 刘敏丰, 高志光, 秦环龙. 生长激素和谷氨酰胺对脓毒症大鼠细胞因子和氨基酸代谢的影响 [J]. 中国普外基础与临床杂志, 2006; 13(5): 535-539.
35. 梁志刚, 刘锡麟, 李江, 等. 重组人生长激素对重度烧伤后细胞因子的影响 [J]. 中华烧伤杂志, 2002; 18(1): 49-51.
36. Sodhi A, Tripathi A. Prolactin and growth hormone induce differential cytokine and chemokine profile in murine peritoneal macrophages in vitro: involvement of p-38 MAP kinase, STAT3 and NF-kappaB [J]. Cytokine, 2008; 41(2): 162-173.
37. 潘云萍, 钟湧, 李建华, 等. 严重创伤后肠黏膜屏障损伤及生长激素治疗作用的临床研究 [J]. 中国危重病急救医学, 2007; 19(8): 496.
38. 黄鹏, 熊炯炘, 王春友, 等. 生长激素和生长抑素联合应用对重症急性胰腺炎患者肠黏膜屏障保护作用的研究 [J]. 临床外科杂志, 2007; 15(3): 178-180.
39. 刘波, 邓宇, 许瑞云. 谷氨酰胺与重组人生长激素对肝硬化患者肠黏膜屏障的影响 [J]. 医学临床研究, 2006; 23(10): 1598-1600.
40. 汤照峰，凌云彪，郝峥, 等. Gln和rhGH对门脉高压症术后肠粘膜屏障及增殖细胞核抗原表达的影响 [J]. 中国病理生理杂志, 2006; 22(9)： 1825-1828.
41. 佟大年，杨俊，秦环龙. 生长激素及谷氨酰胺强化的肠外营养治疗对外科重症患者机体组成及肠屏障功能的影响 [J]. 中国临床营养杂志, 2006; 14(5)： 289-295.
42. 王大庆, 陈静, 万勇. 乌司他丁和生长激素联合应用改善严重腹腔感染合并呼吸循环功能障碍患者的疗效观察 [J]. 中国普外基础与临床杂志, 2008; 15(4): 283-284.
43. Takala J, Ruokonen E, Webster NR， et al． Increased mortality associated with growth hormone treatment in critically ill adults [J]． N Engl J Med, 1999; 341(11): 785-792.
44. 周建平，刘祺. 生长激素对人结肠癌细胞作用的研究 [J]. 中国普外基础与临床杂志, 2005; 12(4): 390-392.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effects of Recombinant Human Growth Hormone on Intestinal Barrier Function

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