• 上海交通大學(xué)附屬第六人民醫(yī)院普外科（上海 200233）;

目的探討應(yīng)用外源性胃促生長(zhǎng)素（ghrelin）對(duì)胃大部切除術(shù)后大鼠早期恢復(fù)的影響。方法將12只胃大部切除（畢Ⅰ式）大鼠隨機(jī)均分為2組，分別于腹腔內(nèi)注射生理鹽水或胃促生長(zhǎng)素，稱量術(shù)前和術(shù)后1～7 d的大鼠體重和每日攝食量； 術(shù)后第7天處死大鼠，實(shí)時(shí)熒光定量PCR法測(cè)定大鼠胃底組織中胃促生長(zhǎng)素mRNA表達(dá)相對(duì)量，并檢測(cè)吻合口爆破壓和吻合口組織中羥脯氨酸含量。結(jié)果2組大鼠之間術(shù)前及術(shù)后1～7 d體重的差異均無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05）。生理鹽水組大鼠體重術(shù)后逐漸降低，并均明顯低于術(shù)前（P lt;0.01），且在術(shù)后第5天達(dá)到最低（P lt;0.01），后逐漸增加，但仍均低于術(shù)前（P lt;0.01）； 胃促生長(zhǎng)素組大鼠體重術(shù)后逐漸降低，除術(shù)后1 d與術(shù)前比較的差異無(wú)統(tǒng)計(jì)學(xué)意義（P=0.693）外，均明顯低于術(shù)前（P lt;0.01）， 在術(shù)后第4天達(dá)到最低（P lt;0.01），后逐漸增加，但仍均低于術(shù)前（P lt;0.05或P lt;0.01）。胃促生長(zhǎng)素組大鼠的累積攝食量為（52.50±6.77） g，明顯高于生理鹽水組大鼠的(45.67±7.47) g，P lt;0.05。術(shù)后第7天胃促生長(zhǎng)素組大鼠胃底組織中胃促生長(zhǎng)素mRNA表達(dá)相對(duì)量為0.08±0.04，明顯低于生理鹽水組大鼠的0.22±0.07（P lt;0.01）。胃促生長(zhǎng)素組大鼠吻合口爆破壓為（172.33±10.44） mm Hg（1 mm Hg=0.133 kPa）， 明顯高于生理鹽水組的(155.83±6.62) mm Hg，P lt;0.05。胃促生長(zhǎng)素組大鼠吻合口組織中羥脯氨酸含量為（0.50±0.29）μg/mg wet tissue，明顯高于生理鹽水組大鼠的(0.43±0.05) μg/mg wet tissue，P lt;0.01。結(jié)論胃促生長(zhǎng)素能有效促進(jìn)胃大部切除術(shù)后大鼠的早期恢復(fù)，而外源性胃促生長(zhǎng)素的攝入可抑制機(jī)體術(shù)后早期的負(fù)反饋性代償作用。

引用本文： 于嵩,王志剛,楊成廣,閻鈞,鄭起. 胃促生長(zhǎng)素對(duì)胃大部切除大鼠術(shù)后早期恢復(fù)的影響. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(7): 728-731. doi: 復(fù)制

1. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growthhormonereleasing acylated peptide from stomach [J]. Nature, 1999, 402(6762): 656660.
2. Ueno H, Yamaguchi H, Kangawa K, et al. Ghrelin: a gastric peptide that regulates food intake and energy homeostasis [J]. Regul Pept, 2005, 126(12): 1119.
3. Date Y, Murakami N, Toshinai K, et al. The role of the gastric afferent vagal nerve in ghrelininduced feeding and growth hormone secretion in rats [J]. Gastroenterology, 2002, 123(4): 11201128.
4. 王維剛, 王志剛, 張永彥, 等. 生長(zhǎng)激素促分泌素受體基因敲除小鼠胚胎干細(xì)胞的建立 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(10): 733738.
5. Kojima M, Kangawa K. Ghrelin: structure and function [J]. Physiol Rev, 2005, 85(2): 495522.
6. Kojima M, Kangawa K. Ghrelin: more than endogenous growth hormone secretagogue [J]. Ann N Y Acad Sci, 2010, 1200(1): 140148.
7. Kiyama T, Mizutani T, Okuda T, et al. Postoperative changes in body composition after gastrectomy [J]. J Gastrointest Surg, 2005, 9(3): 313319.
8. 蘇丹, 蘭平, 任東林, 等. 小承氣合劑促進(jìn)結(jié)腸吻合術(shù)后吻合口組織愈合的實(shí)驗(yàn)研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(1): 3942.
9. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2Delta Delta CT Method [J]. Methods, 2001, 25(4): 402408.
10. Schefe JH, Lehmann KE, Buschmann IR, et al. Quantitative realtime RTPCR data analysis: current concepts and the novel “gene expression’s CT difference” formula [J]. J Mol Med, 2006, 84(11): 901910.
11. Cowley MA, Smith RG, Diano S, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis [J]. Neuron, 2003, 37(4): 649661.
12. Toshinai K, Date Y, Murakami N, et al. Ghrelininduced food intake is mediated via the orexin pathway [J]. Endocrinology, 2003, 144(4): 15061512.
13. Tschp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents [J]. Nature, 2000, 407(6806): 908913.
14. Wren AM, Small CJ, Abbott CR, et al. Ghrelin causes hyperphagia and obesity in rats [J]. Diabetes, 2001, 50(11): 25402547.
15. Wang HT, Lu QC, Wang Q, et al. Role of the duodenum in regulation of plasma ghrelin levels and body mass index after subtotal gastrectomy [J]. World J Gastroenterol, 2008, 14(15): 24252429.
16. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after dietinduced weight loss or gastric bypass surgery [J]. N Engl J Med, 2002, 346(21): 16231630.
17. Dornonville de la Cour C, Bjrkqvist M, Sandvik AK, et al. Alike cells in the rat stomach contain ghrelin and do not operate under gastrin control [J]. Regul Pept, 2001, 99(23): 141150.
18. Dornonville de la Cour C, Lindqvist A, Egecioglu E, et al. Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice [J]. Gut, 2005, 54(7): 907913.
19. Takachi K, Doki Y, Ishikawa O, et al. Postoperative ghrelin levels and delayed recovery from body weight loss after distal or total gastrectomy [J]. J Surg Res, 2006, 130(1): 17.
20. de Hingh IH, Siemonsma MA, de Man BM, et al. The matrix metalloproteinase inhibitor BB94 improves the strength of intestinal anastomoses in the rat [J]. Int J Colorectal Dis, 2002, 17(5): 348354.
21. 李占武, 王利, 李方毅, 等. 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 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(11): 11411146.
22. Lanfranco F, Motta G, Baldi M, et al. Ghrelin and anterior pituitary function [J]. Front Horm Res, 2010, 38: 206211.
23. Hataya Y, Akamizu T, Takaya K, et al. A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GHreleasing hormone in humans [J]. J Clin Endocrinol Metab, 2001, 86(9): 4552.
24. Dixit VD, Schaffer EM, Pyle RS, et al. Ghrelin inhibits leptin and activationinduced proinflammatory cytokine expression by human monocytes and T cells [J]. J Clin Invest, 2004, 114(1): 5766.
25. De Smet B, Thijs T, Moechars D, et al. Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphateinduced colitis in mice [J]. Neurogastroenterol Motil, 2009, 21(1): 5970.
26. Brzozowski T, Konturek PC, Sliwowski Z, et al. Prostaglandin/cyclooxygenase pathway in ghrelininduced gastroprotection against ischemiareperfusion injury [J]. J Pharmacol Exp Ther, 2006, 319(1): 477487.
27. Konturek PC, Brzozowski T, Konturek SJ, et al. Role of histamine in ghrelininduced gastroprotection against acute gastric lesions [J]. Inflamm Res, 2007, 56 Suppl 1: S25S26.
  1. 1. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growthhormonereleasing acylated peptide from stomach [J]. Nature, 1999, 402(6762): 656660.
  2. 2. Ueno H, Yamaguchi H, Kangawa K, et al. Ghrelin: a gastric peptide that regulates food intake and energy homeostasis [J]. Regul Pept, 2005, 126(12): 1119.
  3. 3. Date Y, Murakami N, Toshinai K, et al. The role of the gastric afferent vagal nerve in ghrelininduced feeding and growth hormone secretion in rats [J]. Gastroenterology, 2002, 123(4): 11201128.
  4. 4. 王維剛, 王志剛, 張永彥, 等. 生長(zhǎng)激素促分泌素受體基因敲除小鼠胚胎干細(xì)胞的建立 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2008, 15(10): 733738.
  5. 5. Kojima M, Kangawa K. Ghrelin: structure and function [J]. Physiol Rev, 2005, 85(2): 495522.
  6. 6. Kojima M, Kangawa K. Ghrelin: more than endogenous growth hormone secretagogue [J]. Ann N Y Acad Sci, 2010, 1200(1): 140148.
  7. 7. Kiyama T, Mizutani T, Okuda T, et al. Postoperative changes in body composition after gastrectomy [J]. J Gastrointest Surg, 2005, 9(3): 313319.
  8. 8. 蘇丹, 蘭平, 任東林, 等. 小承氣合劑促進(jìn)結(jié)腸吻合術(shù)后吻合口組織愈合的實(shí)驗(yàn)研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2011, 18(1): 3942.
  9. 9. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2Delta Delta CT Method [J]. Methods, 2001, 25(4): 402408.
  10. 10. Schefe JH, Lehmann KE, Buschmann IR, et al. Quantitative realtime RTPCR data analysis: current concepts and the novel “gene expression’s CT difference” formula [J]. J Mol Med, 2006, 84(11): 901910.
  11. 11. Cowley MA, Smith RG, Diano S, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis [J]. Neuron, 2003, 37(4): 649661.
  12. 12. Toshinai K, Date Y, Murakami N, et al. Ghrelininduced food intake is mediated via the orexin pathway [J]. Endocrinology, 2003, 144(4): 15061512.
  13. 13. Tschp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents [J]. Nature, 2000, 407(6806): 908913.
  14. 14. Wren AM, Small CJ, Abbott CR, et al. Ghrelin causes hyperphagia and obesity in rats [J]. Diabetes, 2001, 50(11): 25402547.
  15. 15. Wang HT, Lu QC, Wang Q, et al. Role of the duodenum in regulation of plasma ghrelin levels and body mass index after subtotal gastrectomy [J]. World J Gastroenterol, 2008, 14(15): 24252429.
  16. 16. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after dietinduced weight loss or gastric bypass surgery [J]. N Engl J Med, 2002, 346(21): 16231630.
  17. 17. Dornonville de la Cour C, Bjrkqvist M, Sandvik AK, et al. Alike cells in the rat stomach contain ghrelin and do not operate under gastrin control [J]. Regul Pept, 2001, 99(23): 141150.
  18. 18. Dornonville de la Cour C, Lindqvist A, Egecioglu E, et al. Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice [J]. Gut, 2005, 54(7): 907913.
  19. 19. Takachi K, Doki Y, Ishikawa O, et al. Postoperative ghrelin levels and delayed recovery from body weight loss after distal or total gastrectomy [J]. J Surg Res, 2006, 130(1): 17.
  20. 20. de Hingh IH, Siemonsma MA, de Man BM, et al. The matrix metalloproteinase inhibitor BB94 improves the strength of intestinal anastomoses in the rat [J]. Int J Colorectal Dis, 2002, 17(5): 348354.
  21. 21. 李占武, 王利, 李方毅, 等. 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 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(11): 11411146.
  22. 22. Lanfranco F, Motta G, Baldi M, et al. Ghrelin and anterior pituitary function [J]. Front Horm Res, 2010, 38: 206211.
  23. 23. Hataya Y, Akamizu T, Takaya K, et al. A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GHreleasing hormone in humans [J]. J Clin Endocrinol Metab, 2001, 86(9): 4552.
  24. 24. Dixit VD, Schaffer EM, Pyle RS, et al. Ghrelin inhibits leptin and activationinduced proinflammatory cytokine expression by human monocytes and T cells [J]. J Clin Invest, 2004, 114(1): 5766.
  25. 25. De Smet B, Thijs T, Moechars D, et al. Endogenous and exogenous ghrelin enhance the colonic and gastric manifestations of dextran sodium sulphateinduced colitis in mice [J]. Neurogastroenterol Motil, 2009, 21(1): 5970.
  26. 26. Brzozowski T, Konturek PC, Sliwowski Z, et al. Prostaglandin/cyclooxygenase pathway in ghrelininduced gastroprotection against ischemiareperfusion injury [J]. J Pharmacol Exp Ther, 2006, 319(1): 477487.
  27. 27. Konturek PC, Brzozowski T, Konturek SJ, et al. Role of histamine in ghrelininduced gastroprotection against acute gastric lesions [J]. Inflamm Res, 2007, 56 Suppl 1: S25S26.