• 1.蘭州大學(xué)研究生院第一臨床醫(yī)學(xué)院大外ICU(甘肅蘭州 730000);;
  • 2.上海市松江區(qū)中心醫(yī)院急診內(nèi)科和ICU（上海 201600）;;
  • 3.蘭州大學(xué)研究生院第一臨床醫(yī)學(xué)院影像學(xué)(甘肅蘭州730000);;
  • 4.廣州醫(yī)學(xué)院研究生院第二附屬醫(yī)院神經(jīng)外科學(xué)(廣東廣州　510260);

目的探討持續(xù)區(qū)域動(dòng)脈灌注(CRAI)地塞米松對(duì)重癥急性胰腺炎(SAP)家兔血清炎性因子的影響及治療效果。方法采用胰腺被膜下注射5%牛磺膽酸鈉制備SAP家兔模型。采用隨機(jī)數(shù)字表法將24只家兔隨機(jī)分為假手術(shù)組、SAP組、靜脈灌注地塞米松組及CRAI地塞米松組(每組6只)。造模成功后0.5、3、6、9及12 h檢測各組血清腫瘤壞死因子(TNF)α、白介素(IL)6、IL-10及淀粉酶(AMY)水平，并觀察家兔胰腺病理變化和生存情況。結(jié)果與假手術(shù)組相比，SAP組家兔血清IL-6水平在造模成功后3 h明顯升高，在6 h達(dá)到高峰，9 h開始下降(均P lt;0.05); IL-10水平在6 h時(shí)開始顯著升高，且9 h及12 h時(shí)均持續(xù)升高(均P lt;0.001); TNF-α水平在0.5 h已經(jīng)顯著升高，6 h達(dá)到高峰，9 h開始下降(均P lt;0.05); AMY在9 h開始升高，至12 h時(shí)仍持續(xù)升高(均P lt;0.05)。與SAP組相比，CRAI地塞米松組血清IL-6及IL-10水平在6、9及12 h時(shí)均明顯降低(P lt;0.001)，靜脈灌注地塞米松組3 h以后的各時(shí)段血清IL-6水平降低，但僅在6 h時(shí)差異具有統(tǒng)計(jì)學(xué)意義(P lt;0.05)； CRAI地塞米松組TNF-α水平在3 h就已經(jīng)開始明顯降低(P lt;0.001)，此后各時(shí)段均明顯持續(xù)降低(P lt;0.001)，而靜脈灌注地塞米松組血清TNF-α水平僅在6 h顯著降低(P lt;0.05)； CRAI地塞米松組和靜脈灌注地塞米松組血清AMY在12 h時(shí)均顯著降低(P lt;0.05)。與靜脈灌注地塞米松組相比，CRAI地塞米松組血清IL-6和IL-10水平在6 h(P lt;0.05)及12 h(P lt;0.001)時(shí)明顯降低; TNF-α水平在3、6、9及12 h均明顯降低(P lt;0.001)； AMY變化差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05)。CRAI地塞米松組胰腺組織損害明顯改善，3 d時(shí)動(dòng)物死亡明顯減少。結(jié)論CRAI地塞米松能夠減輕SAP家兔的全身炎癥反應(yīng)和胰腺局部的炎癥反應(yīng)，改善動(dòng)物生存情況。

引用本文： 涂巧麗,張世龍,石斌,劉宏,曹文英. 地塞米松區(qū)域動(dòng)脈灌注治療重癥急性胰腺炎的實(shí)驗(yàn)研究. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(12): 1278-1282. doi: 復(fù)制

1. Hirota M, Nozawa F, Okabe A, et al. Relationship between plasma cytokine concentration and multiple organ failure in patients with acute pancreatitis [J]. Pancreas, 2000, 21(2): 141146.
2. Office of Laboratory Animal Welfare. Public health service policy on humane care and use of laboratory animals [Z]. http://grants.nih.gov/grants/olaw/olaw.htm.
3. Jacobs ML, Daggett WM, Civette JM, et al. Acute pancreatitis: analysis of factors influencing survival [J]. Ann Surg, 1977, 185(1): 4351.
4. Waage A, Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharidestimulated human monocytes [J]. Immunology, 1988, 63(2): 299302.
5. Nakagawa M, Bondy GP, Waisman D, et al. The effect of glucocorticoids on the expression of Lselectin on polymorphonuclear leukocyte [J]. Blood, 1999, 93(8): 27302737.
6. Galon J, Franchimont D, Hiroi N, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells [J]. FASEB J, 2002, 16(1): 6171.
7. Ramírez F, Fowell DJ, Puklavec M, et al. Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro [J]. J Immunol, 1996, 156(7): 24062412.
8. Yubero S, Ramudo L, Manso MA, et al. Mechanisms of dexamethasonemediated chemokine downregulation in mild and severe acute pancreatitis [J]. Biochim Biophys Acta, 2009, 1792(12): 12051211.
9. Wan MH, Li J, Gong HL, et al. Clinical observation on the effect of dexamethasone and Chinese herbal decoction for purgation in severe acute pancreatitis patients [J]. Chin J Integr Med, 2011, 17(2): 141145.
10. Ramudo L, Yubero S, Manso MA, et al. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats [J]. Pancreas, 2010, 39(7): 10571063.
11. Ramudo L, Yubero S, Manso MA, et al. Effect of dexamethasone on peripheral blood leukocyte immune response in bilepancreatic duct obstructioninduced acute pancreatitis [J]. Steroids, 2010, 75(45): 362367.
12. Zhang XP, Pan Y, Huang XM, et al. Effects of dexamethasone and Salvia miltiorrhizae on the small intestine and immune organs of rats with severe acute pancreatitis [J]. Inflammation, 2010, 33(4): 259266.
13. Rook GA. Glucocorticoids and immune function [J]. Baillieres Best Pract Res Clin Endocrinol Metab, 1999, 13(4): 567581.
14. Sherman S, Blaut U, Watkins JL, et al. Does prophylactic administration of corticosteroid reduce the risk and severity of postERCP pancreatitis: a randomized, prospective, multicenter study [J]. Gastrointest Endosc, 2003, 58(1): 2329.
15. 成蘭． 應(yīng)用地塞米松的不良反應(yīng)與注意事項(xiàng) [J]. 中原醫(yī)刊， 2002， 29(11): 4849．.
16. Weiner GR, Geenen JE, Hogan WJ, et al. Use of corticosteroids in the prevention of postERCP pancreatitis [J]. Gastrointest Endosc, 1995, 42(6): 579583.
17. Osman MO, Jensen SL. Acute pancreatitis: the pathophysiological role of cytokines and integrins. New trends for treatment? [J]. Dig Surg, 1999, 16(5): 347362.
18. Satoh A, Gukovskaya AS, Edderkaoui M, et al. Tumor necrosis factoralpha mediates pancreatitis responses in acinar cells via protein kinase C and prolinerich tyrosine kinase 2 [J]. Gastroenterology, 2005, 129(2): 639651.
19. Xue DB, Zhang WH, Yun XG, et al. Regulating effects of Arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats [J]. Chin Med J, 2007, 120(8): 690695.
20. 白斗， 王東． 急性胰腺炎發(fā)病機(jī)制中炎性因子的作用研究進(jìn)展 [J]. 吉林醫(yī)學(xué)， 2011， 32(3): 572573．.
21. 徐延均， 吳新民， 郭亞民． 腫瘤壞死因子α及白介素在急性胰腺炎中的作用 [J]. 中國普外基礎(chǔ)與臨床雜志， 2010， 17(9): 993996．.
22. Stellato C, Beck LA, Gorgone GA, et al. Expression of the chemokine RANTES by a human bronchial epithelial cell line. Modulation by cytokines and glucocorticoids [J]. J Immunol, 1995, 155(1): 410418.
23. Kyriakides C, Jasleen J, Wang Y, et al. Neutrophils, not complement, mediate the mortality of experimental hemorrhagic pancreatitis [J]. Pancreas, 2001, 22(1): 4046.
24. Pastor CM, Vonlaufen A, Georgi F, et al. Neutrophil depletion-but not prevention of Kupffer cell activation－decreases the severity of ceruleininduced acute pancreatitis [J]. World J Gastroenterol, 2006, 12(8): 12191224.
  1. 1. Hirota M, Nozawa F, Okabe A, et al. Relationship between plasma cytokine concentration and multiple organ failure in patients with acute pancreatitis [J]. Pancreas, 2000, 21(2): 141146.
  2. 2. Office of Laboratory Animal Welfare. Public health service policy on humane care and use of laboratory animals [Z]. http://grants.nih.gov/grants/olaw/olaw.htm.
  3. 3. Jacobs ML, Daggett WM, Civette JM, et al. Acute pancreatitis: analysis of factors influencing survival [J]. Ann Surg, 1977, 185(1): 4351.
  4. 4. Waage A, Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharidestimulated human monocytes [J]. Immunology, 1988, 63(2): 299302.
  5. 5. Nakagawa M, Bondy GP, Waisman D, et al. The effect of glucocorticoids on the expression of Lselectin on polymorphonuclear leukocyte [J]. Blood, 1999, 93(8): 27302737.
  6. 6. Galon J, Franchimont D, Hiroi N, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells [J]. FASEB J, 2002, 16(1): 6171.
  7. 7. Ramírez F, Fowell DJ, Puklavec M, et al. Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro [J]. J Immunol, 1996, 156(7): 24062412.
  8. 8. Yubero S, Ramudo L, Manso MA, et al. Mechanisms of dexamethasonemediated chemokine downregulation in mild and severe acute pancreatitis [J]. Biochim Biophys Acta, 2009, 1792(12): 12051211.
  9. 9. Wan MH, Li J, Gong HL, et al. Clinical observation on the effect of dexamethasone and Chinese herbal decoction for purgation in severe acute pancreatitis patients [J]. Chin J Integr Med, 2011, 17(2): 141145.
  10. 10. Ramudo L, Yubero S, Manso MA, et al. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats [J]. Pancreas, 2010, 39(7): 10571063.
  11. 11. Ramudo L, Yubero S, Manso MA, et al. Effect of dexamethasone on peripheral blood leukocyte immune response in bilepancreatic duct obstructioninduced acute pancreatitis [J]. Steroids, 2010, 75(45): 362367.
  12. 12. Zhang XP, Pan Y, Huang XM, et al. Effects of dexamethasone and Salvia miltiorrhizae on the small intestine and immune organs of rats with severe acute pancreatitis [J]. Inflammation, 2010, 33(4): 259266.
  13. 13. Rook GA. Glucocorticoids and immune function [J]. Baillieres Best Pract Res Clin Endocrinol Metab, 1999, 13(4): 567581.
  14. 14. Sherman S, Blaut U, Watkins JL, et al. Does prophylactic administration of corticosteroid reduce the risk and severity of postERCP pancreatitis: a randomized, prospective, multicenter study [J]. Gastrointest Endosc, 2003, 58(1): 2329.
  15. 15. 成蘭． 應(yīng)用地塞米松的不良反應(yīng)與注意事項(xiàng) [J]. 中原醫(yī)刊， 2002， 29(11): 4849．.
  16. 16. Weiner GR, Geenen JE, Hogan WJ, et al. Use of corticosteroids in the prevention of postERCP pancreatitis [J]. Gastrointest Endosc, 1995, 42(6): 579583.
  17. 17. Osman MO, Jensen SL. Acute pancreatitis: the pathophysiological role of cytokines and integrins. New trends for treatment? [J]. Dig Surg, 1999, 16(5): 347362.
  18. 18. Satoh A, Gukovskaya AS, Edderkaoui M, et al. Tumor necrosis factoralpha mediates pancreatitis responses in acinar cells via protein kinase C and prolinerich tyrosine kinase 2 [J]. Gastroenterology, 2005, 129(2): 639651.
  19. 19. Xue DB, Zhang WH, Yun XG, et al. Regulating effects of Arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats [J]. Chin Med J, 2007, 120(8): 690695.
  20. 20. 白斗， 王東． 急性胰腺炎發(fā)病機(jī)制中炎性因子的作用研究進(jìn)展 [J]. 吉林醫(yī)學(xué)， 2011， 32(3): 572573．.
  21. 21. 徐延均， 吳新民， 郭亞民． 腫瘤壞死因子α及白介素在急性胰腺炎中的作用 [J]. 中國普外基礎(chǔ)與臨床雜志， 2010， 17(9): 993996．.
  22. 22. Stellato C, Beck LA, Gorgone GA, et al. Expression of the chemokine RANTES by a human bronchial epithelial cell line. Modulation by cytokines and glucocorticoids [J]. J Immunol, 1995, 155(1): 410418.
  23. 23. Kyriakides C, Jasleen J, Wang Y, et al. Neutrophils, not complement, mediate the mortality of experimental hemorrhagic pancreatitis [J]. Pancreas, 2001, 22(1): 4046.
  24. 24. Pastor CM, Vonlaufen A, Georgi F, et al. Neutrophil depletion-but not prevention of Kupffer cell activation－decreases the severity of ceruleininduced acute pancreatitis [J]. World J Gastroenterol, 2006, 12(8): 12191224.