• 首都醫(yī)科大學(xué)宣武醫(yī)院普外科（北京 100053）;

目的  總結(jié)重癥急性胰腺炎(SAP)時腸屏障功能障礙(IBD)的發(fā)病機(jī)理、檢測方法及治療進(jìn)展。
方法 復(fù)習(xí)近年來國內(nèi)、外有關(guān)SAP 時IBD方面的文獻(xiàn)并進(jìn)行綜述。
結(jié)果  SAP時IBD的發(fā)病機(jī)理涉及多個環(huán)節(jié)，缺血/再灌注損傷、內(nèi)毒素、炎癥介質(zhì)、胃腸激素等起關(guān)鍵作用。IBD的檢測有多種方法，尿乳果糖/甘露醇比值和血漿二胺氧化酶是相對理想的指標(biāo)。積極治療SAP，維持腸道灌注是治療IBD的基礎(chǔ)，并在此基礎(chǔ)上合理運(yùn)用促胃腸動力藥、營養(yǎng)支持、中藥等治療。
結(jié)論  IBD是一個復(fù)雜的病理生理過程，近年來大量動物實(shí)驗(yàn)和臨床研究結(jié)果為其的防治提供了新思路，但具體參與其中的細(xì)胞、分子的作用機(jī)理有待于進(jìn)一步研究。

引用本文： 刁永鵬,陳宏,李非. 重癥急性胰腺炎腸屏障功能障礙的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(7): 588-592. doi: 復(fù)制

1. Liu H, Li W, Wang X, et al. Early gut mucosal dysfunction in patients with acute pancreatitis [J]. Pancreas, 2008; 36(2)： 192196.
2. Thuijls G, Haan JJ, Derikx JP, et al. Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock [J]. Shock, 2009; 31(2)： 164169.
3. 劉震, 程若川, 方向, 等. PAAF與ASPAAF誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(8)： 555559.
4. Diebel LN, Liberati DM, Baylor AE 3rd, et al. The pivotal role of tumor necrosis factoralpha in signaling apoptosis in intestinal epithelial cells under shock conditions [J]. J Trauma, 2005; 58(5)： 9951001.
5. Bock J, Liebisch G, Schweimer J, et al. Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function [J]. World J Gastroenterol, 2007; 13(39)： 52175225.
6. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa [J]. Physiol Rev, 2007; 87(2)： 545564.
7. Li Q, Zhang Q, Wang M, et al. Interferonγ and tumor necrosis factorα disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction [J]. Clin Immunol, 2008; 126(1)： 6780.
8. Boivin MA, Roy PK, Bradley A, et al. Mechanism of interferonγinduced increase in T84 intestinal epithelial tight junction [J]. J Interferon Cytokine Res, 2009; 29(1)： 4554.
9. Bhatia M. Inflammatory response on the pancreatic acinar cell injury [J]. Scand J Surg, 2005; 94(2)： 97102.
10. Zayat M, Lichtenberger LM, Dial EJ. Pathophysiology of LPSinduced gastrointestinal injury in the rat: role of secretory phospholipase A2 [J]. Shock, 2008; 30(2)： 206211.
11. Maeda H, Akaike T, Yoshida M, et al. Multiple functions of nitric oxide in pathophysiology and microbiology: analysis by a new nitric oxide scavenger [J]. J Leukoc Biol, 1994; 56(5)： 588592.
12. Smail N, Catania RA, Wang P, et al. Gut and liver: the organs responsible for increased nitric oxide production after traumahemorrhage and resuscitation [J]. Arch Surg, 1998; 133(4)： 399405.
13. Vallance BA, Dijkstra G, Qiu B, et al. Relative contributions of NOS isoforms during experimental colitis: endothelialderived NOS maintains mucosal integrity [J]. Am J Physiol Gastrointest Liver Physiol, 2004; 287(4)： G865G874.
14. Marc Rhoads J, Wu G. Glutamine, arginine, and leucine signaling in the intestine [J]. Amino Acids, 2009; 37(1): 111112.
15. Avgerinos C, Delis S, Rizos S, et al. Nutritional support in acute pancreatitis [J]. Dig Dis, 2003; 21(3)： 214219.
16. Wang X, Gong Z, Wu K, et al. Gastrointestinal dysmotility in patients with acute pancreatitis [J]. J Gastroenterol Hepatol, 2003; 18(1)： 5762.
17. Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs [J]. Chin Med J (Engl), 2006; 119(8)： 656661.
18. 何桂珍, 崔曉雨, 董良廣, 等. 大鼠腸道缺血/再灌注時腸淋巴干結(jié)扎對腸道屏障的影響 [J]. 中國臨床營養(yǎng)雜志, 2007; 15(3)： 155159.
19. Luyer MD, Buurman, WA, Hadfoune M, et al. Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic inflammation and gut barrier loss via an IFNγ dependent route [J]. Ann Surg, 2007; 245(5)： 795802.
20. 王興鵬, 王冰嫻, 吳愷, 等. 細(xì)胞凋亡在急性壞死型胰腺炎早期腸黏膜上皮細(xì)胞死亡中的作用 [J]. 中華消化雜志, 2001; 21(5)： 267270.
21. Sun XQ, Fu XB, Zhang R, et al. Relationship between plasma D()lactate and intestinal damage after severe injuries in rats [J]. World J Gastroenterol, 2001; 7(4)： 555558.
22. 黎君友, 呂藝, 付小兵, 等. 二胺氧化酶在創(chuàng)傷后腸道損傷中變化及意義 [J]. 中國危重病急救醫(yī)學(xué), 2000; 12(8)： 482484.
23. Theodoropoulos G, Lloyd LR, Cousins G, et al. Intraoperative and early postoperative gastric intramucosal pH predicts morbidity and mortality after major abdominal surgery [J]. Am Surg, 2001; 67(4)： 303308.
24. Ammori BJ, Becker KL, Kite P, et al. Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis [J]. Pancreas, 2003; 27(3)： 239243.
25. Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis [J]. J Gastrointest Surg, 2003; 7(1)： 2635.
26. 程禮, 王興鵬, 汪佩文, 等. 保護(hù)腸屏障功能對重癥急性胰腺炎患者預(yù)后的影響 [J]. 胃腸病學(xué), 2005; 10(1)： 2426.
27. 中華醫(yī)學(xué)會消化病學(xué)分會. 腸屏障功能障礙臨床診治建議 [J]. 中華消化雜志, 2006; 26(9)： 620.
28. Higuchi S, Wu R, Zhou M, et al. Gut hyperpermiability after ischemia and reperfusion:attenuation with adrenomedullin and its binding protein treatment [J]. Int J Clin Exp Pathol, 2008; 1(5)： 409418.
29. Costantini TW, Loomis WH, Putnam JG, et al. Pentoxifylline modulates intestinal tight junction signaling after burn injury: effects on myosin light chain kinase [J]. J Trauma, 2009; 66(1)： 1724.
30. Ko JS, Yang HR, Chang JY, et al. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin8 secretion induced by tumor necrosis factorα [J]. World J Gastroenterol, 2007; 13(13)： 19621965.
31. Qin HL, Shen TY, Gao ZG, et al. Effect of lactobacillus on the gut microflora and barrier function of the rats with abdominal infection [J]. World J Gastroenterol, 2005; 11(17)： 25912596.
32. Kim Y, Kim SH, Whang KY, et al. Inhibition of escherichia coli O157: H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells [J]. J Microbiol Biotechnol, 2008; 18(7)： 12781285.
33. Wang Z, Xiao G, Yao Y, et al. The role of bifidobacteria in gut barrier function after thermal injury in rats [J]. J Trauma, 2006; 61(3)： 650657.
34. Besselink MG, Timmerman HM, Minnen LP, et al. Prevention of infectious complications in surgical patients: potential role of probiotics [J]. Dig Surg, 2005; 22(4)： 234244.
35. 陳宏, 賈建國, 李非, 等. 腸內(nèi)營養(yǎng)對重癥急性胰腺炎預(yù)后的影響 [J]. 中國臨床營養(yǎng)雜志, 2006; 14(1)： 3739.
36. Shen TY, Qin HL, Gao ZG, et al. Influences of enteral nutrition combined with probiotics on gut microflora and barrier function of rats with abdominal infection [J]. World J Gastroenterol, 2006; 12(27)： 43524358.
37. 余利堅， 徐亮， 姚暉， 等. 腸內(nèi)免疫營養(yǎng)和生態(tài)營養(yǎng)對創(chuàng)傷后大鼠腸屏障功能的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(11)： 794798.
38. Briassoulis G, Filippou O, Hatzi E, et al. Early enteral administration of immunonutrition in critically ill children: results of a blinded randomized controlled clinical trial [J]. Nutrition, 2005; 21(78)： 799807.
39. 董亮， 康焰. 早期腸內(nèi)營養(yǎng)在重癥急性胰腺炎治療中的應(yīng)用 [J]. 中國普外基礎(chǔ)與臨床雜志， 2008; 15(8)： 567571.
40. 劉波, 喬穎欣, 周家駒. 瀉下藥和解表藥的現(xiàn)代藥理解釋 [J]. 中國藥學(xué)雜志, 2007; 42(6)： 422426.
41. 鄧群, 黎沾良, 陳連榮, 等. 生長抑素減輕大鼠急性壞死性胰腺炎的腸屏障損害 [J]. 中華普通外科雜志, 2000; 15(12)： 752754.
42. Nighot PK, Moeser AJ, Ryan KA, et al. ClC2 is required for rapid restoration of epithelial tight junctions in ischemicinjured murine jejunum [J]. Exp Cell Res, 2009; 315(1)： 110118.
43. Leveau P, Wang X, Sun Z, et al. Severity of pancreatitisassociated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant [J]. Biochem Pharmacol, 2005; 69(9)： 13251331.
44. Zhang F, Tong L, Qiao H, et al. Taurine attenuates multiple organ injury induced by intestinal ischemia reperfusion in rats [J]. J Surg Res, 2008; 149(1)： 101109.
  1. 1. Liu H, Li W, Wang X, et al. Early gut mucosal dysfunction in patients with acute pancreatitis [J]. Pancreas, 2008; 36(2)： 192196.
  2. 2. Thuijls G, Haan JJ, Derikx JP, et al. Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock [J]. Shock, 2009; 31(2)： 164169.
  3. 3. 劉震, 程若川, 方向, 等. PAAF與ASPAAF誘導(dǎo)的腸損傷比較的實(shí)驗(yàn)研究 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(8)： 555559.
  4. 4. Diebel LN, Liberati DM, Baylor AE 3rd, et al. The pivotal role of tumor necrosis factoralpha in signaling apoptosis in intestinal epithelial cells under shock conditions [J]. J Trauma, 2005; 58(5)： 9951001.
  5. 5. Bock J, Liebisch G, Schweimer J, et al. Exogenous sphingomyelinase causes impaired intestinal epithelial barrier function [J]. World J Gastroenterol, 2007; 13(39)： 52175225.
  6. 6. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa [J]. Physiol Rev, 2007; 87(2)： 545564.
  7. 7. Li Q, Zhang Q, Wang M, et al. Interferonγ and tumor necrosis factorα disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction [J]. Clin Immunol, 2008; 126(1)： 6780.
  8. 8. Boivin MA, Roy PK, Bradley A, et al. Mechanism of interferonγinduced increase in T84 intestinal epithelial tight junction [J]. J Interferon Cytokine Res, 2009; 29(1)： 4554.
  9. 9. Bhatia M. Inflammatory response on the pancreatic acinar cell injury [J]. Scand J Surg, 2005; 94(2)： 97102.
  10. 10. Zayat M, Lichtenberger LM, Dial EJ. Pathophysiology of LPSinduced gastrointestinal injury in the rat: role of secretory phospholipase A2 [J]. Shock, 2008; 30(2)： 206211.
  11. 11. Maeda H, Akaike T, Yoshida M, et al. Multiple functions of nitric oxide in pathophysiology and microbiology: analysis by a new nitric oxide scavenger [J]. J Leukoc Biol, 1994; 56(5)： 588592.
  12. 12. Smail N, Catania RA, Wang P, et al. Gut and liver: the organs responsible for increased nitric oxide production after traumahemorrhage and resuscitation [J]. Arch Surg, 1998; 133(4)： 399405.
  13. 13. Vallance BA, Dijkstra G, Qiu B, et al. Relative contributions of NOS isoforms during experimental colitis: endothelialderived NOS maintains mucosal integrity [J]. Am J Physiol Gastrointest Liver Physiol, 2004; 287(4)： G865G874.
  14. 14. Marc Rhoads J, Wu G. Glutamine, arginine, and leucine signaling in the intestine [J]. Amino Acids, 2009; 37(1): 111112.
  15. 15. Avgerinos C, Delis S, Rizos S, et al. Nutritional support in acute pancreatitis [J]. Dig Dis, 2003; 21(3)： 214219.
  16. 16. Wang X, Gong Z, Wu K, et al. Gastrointestinal dysmotility in patients with acute pancreatitis [J]. J Gastroenterol Hepatol, 2003; 18(1)： 5762.
  17. 17. Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs [J]. Chin Med J (Engl), 2006; 119(8)： 656661.
  18. 18. 何桂珍, 崔曉雨, 董良廣, 等. 大鼠腸道缺血/再灌注時腸淋巴干結(jié)扎對腸道屏障的影響 [J]. 中國臨床營養(yǎng)雜志, 2007; 15(3)： 155159.
  19. 19. Luyer MD, Buurman, WA, Hadfoune M, et al. Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic inflammation and gut barrier loss via an IFNγ dependent route [J]. Ann Surg, 2007; 245(5)： 795802.
  20. 20. 王興鵬, 王冰嫻, 吳愷, 等. 細(xì)胞凋亡在急性壞死型胰腺炎早期腸黏膜上皮細(xì)胞死亡中的作用 [J]. 中華消化雜志, 2001; 21(5)： 267270.
  21. 21. Sun XQ, Fu XB, Zhang R, et al. Relationship between plasma D()lactate and intestinal damage after severe injuries in rats [J]. World J Gastroenterol, 2001; 7(4)： 555558.
  22. 22. 黎君友, 呂藝, 付小兵, 等. 二胺氧化酶在創(chuàng)傷后腸道損傷中變化及意義 [J]. 中國危重病急救醫(yī)學(xué), 2000; 12(8)： 482484.
  23. 23. Theodoropoulos G, Lloyd LR, Cousins G, et al. Intraoperative and early postoperative gastric intramucosal pH predicts morbidity and mortality after major abdominal surgery [J]. Am Surg, 2001; 67(4)： 303308.
  24. 24. Ammori BJ, Becker KL, Kite P, et al. Calcitonin precursors: early markers of gut barrier dysfunction in patients with acute pancreatitis [J]. Pancreas, 2003; 27(3)： 239243.
  25. 25. Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis [J]. J Gastrointest Surg, 2003; 7(1)： 2635.
  26. 26. 程禮, 王興鵬, 汪佩文, 等. 保護(hù)腸屏障功能對重癥急性胰腺炎患者預(yù)后的影響 [J]. 胃腸病學(xué), 2005; 10(1)： 2426.
  27. 27. 中華醫(yī)學(xué)會消化病學(xué)分會. 腸屏障功能障礙臨床診治建議 [J]. 中華消化雜志, 2006; 26(9)： 620.
  28. 28. Higuchi S, Wu R, Zhou M, et al. Gut hyperpermiability after ischemia and reperfusion:attenuation with adrenomedullin and its binding protein treatment [J]. Int J Clin Exp Pathol, 2008; 1(5)： 409418.
  29. 29. Costantini TW, Loomis WH, Putnam JG, et al. Pentoxifylline modulates intestinal tight junction signaling after burn injury: effects on myosin light chain kinase [J]. J Trauma, 2009; 66(1)： 1724.
  30. 30. Ko JS, Yang HR, Chang JY, et al. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin8 secretion induced by tumor necrosis factorα [J]. World J Gastroenterol, 2007; 13(13)： 19621965.
  31. 31. Qin HL, Shen TY, Gao ZG, et al. Effect of lactobacillus on the gut microflora and barrier function of the rats with abdominal infection [J]. World J Gastroenterol, 2005; 11(17)： 25912596.
  32. 32. Kim Y, Kim SH, Whang KY, et al. Inhibition of escherichia coli O157: H7 attachment by interactions between lactic acid bacteria and intestinal epithelial cells [J]. J Microbiol Biotechnol, 2008; 18(7)： 12781285.
  33. 33. Wang Z, Xiao G, Yao Y, et al. The role of bifidobacteria in gut barrier function after thermal injury in rats [J]. J Trauma, 2006; 61(3)： 650657.
  34. 34. Besselink MG, Timmerman HM, Minnen LP, et al. Prevention of infectious complications in surgical patients: potential role of probiotics [J]. Dig Surg, 2005; 22(4)： 234244.
  35. 35. 陳宏, 賈建國, 李非, 等. 腸內(nèi)營養(yǎng)對重癥急性胰腺炎預(yù)后的影響 [J]. 中國臨床營養(yǎng)雜志, 2006; 14(1)： 3739.
  36. 36. Shen TY, Qin HL, Gao ZG, et al. Influences of enteral nutrition combined with probiotics on gut microflora and barrier function of rats with abdominal infection [J]. World J Gastroenterol, 2006; 12(27)： 43524358.
  37. 37. 余利堅， 徐亮， 姚暉， 等. 腸內(nèi)免疫營養(yǎng)和生態(tài)營養(yǎng)對創(chuàng)傷后大鼠腸屏障功能的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(11)： 794798.
  38. 38. Briassoulis G, Filippou O, Hatzi E, et al. Early enteral administration of immunonutrition in critically ill children: results of a blinded randomized controlled clinical trial [J]. Nutrition, 2005; 21(78)： 799807.
  39. 39. 董亮， 康焰. 早期腸內(nèi)營養(yǎng)在重癥急性胰腺炎治療中的應(yīng)用 [J]. 中國普外基礎(chǔ)與臨床雜志， 2008; 15(8)： 567571.
  40. 40. 劉波, 喬穎欣, 周家駒. 瀉下藥和解表藥的現(xiàn)代藥理解釋 [J]. 中國藥學(xué)雜志, 2007; 42(6)： 422426.
  41. 41. 鄧群, 黎沾良, 陳連榮, 等. 生長抑素減輕大鼠急性壞死性胰腺炎的腸屏障損害 [J]. 中華普通外科雜志, 2000; 15(12)： 752754.
  42. 42. Nighot PK, Moeser AJ, Ryan KA, et al. ClC2 is required for rapid restoration of epithelial tight junctions in ischemicinjured murine jejunum [J]. Exp Cell Res, 2009; 315(1)： 110118.
  43. 43. Leveau P, Wang X, Sun Z, et al. Severity of pancreatitisassociated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant [J]. Biochem Pharmacol, 2005; 69(9)： 13251331.
  44. 44. Zhang F, Tong L, Qiao H, et al. Taurine attenuates multiple organ injury induced by intestinal ischemia reperfusion in rats [J]. J Surg Res, 2008; 149(1)： 101109.