Advancement in Intestinal Barrier Dysfunction of Severe Acute Pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DIAO Yongpeng , CHEN Hong , LI Fei

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;

Corresponding author：

Keywords：

Severe acute pancreatitis; Intestinal barrier dysfunction; Bacterial translocation; Endotoxin translocation

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Objective To summarize the recent progress in pathogenetic, diagnostic and therapeutic researches on the intestinal barrier dysfunction (IBD) of severe acute pancreatitis (SAP).
Methods The advancement of IBD in SAP, which was published recently at home and abroad, was collected and reviewed.
Results The pathogenesis of IBD in patients with SAP was complex. Ischemia-reperfusion injury, endotoxin, inflammatory mediators and gastrointestinal hormone played an important role in the process of IBD. There were many ways to detect IBD, and the ratio of lactulose and mannitol, plasma diamine oxidase were relatively ideal markers. Medical therapies, such as treatment of SAP and maintaining the perfusion of intestines, were essential to cure IBD. On this basis, the propulsives, nutritional support and traditional Chinese drugs should be administered reasonably.
Conclusions IBD is a sophisticated process of pathophysiology. In recent years, abundant of animal experiments and clinical researches have provided new clue for prevention and cure of IBD, but further researches are still needed on the mechanism of the cells and molecules implicated.

Citation： DIAO Yongpeng,CHEN Hong,LI Fei. Advancement in Intestinal Barrier Dysfunction of Severe Acute Pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(7): 588-592. doi: Copy

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.	刘震, 程若川, 方向, 等. PAAF与ASPAAF诱导的肠损伤比较的实验研究 [J]. 中国普外基础与临床杂志, 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, 崔晓雨, 董良广, 等. 大鼠肠道缺血/再灌注时肠淋巴干结扎对肠道屏障的影响 [J]. 中国临床营养杂志, 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.	王兴鹏, 王冰娴, 吴恺, 等. 细胞凋亡在急性坏死型胰腺炎早期肠黏膜上皮细胞死亡中的作用 [J]. 中华消化杂志, 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, 吕艺, 付小兵, 等. 二胺氧化酶在创伤后肠道损伤中变化及意义 [J]. 中国危重病急救医学, 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.	程礼, 王兴鹏, 汪佩文, 等. 保护肠屏障功能对重症急性胰腺炎患者预后的影响 [J]. 胃肠病学, 2005; 10(1)： 2426.
27.	中华医学会消化病学分会. 肠屏障功能障碍临床诊治建议 [J]. 中华消化杂志, 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.	陈宏, 贾建国, 李非, 等. 肠内营养对重症急性胰腺炎预后的影响 [J]. 中国临床营养杂志, 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.	余利坚，徐亮，姚晖，等. 肠内免疫营养和生态营养对创伤后大鼠肠屏障功能的影响 [J]. 中国普外基础与临床杂志, 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. 早期肠内营养在重症急性胰腺炎治疗中的应用 [J]. 中国普外基础与临床杂志， 2008; 15(8)： 567571.
40.	刘波, 乔颖欣, 周家驹. 泻下药和解表药的现代药理解释 [J]. 中国药学杂志, 2007; 42(6)： 422426.
41.	邓群, 黎沾良, 陈连荣, 等. 生长抑素减轻大鼠急性坏死性胰腺炎的肠屏障损害 [J]. 中华普通外科杂志, 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. 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. 刘震, 程若川, 方向, 等. PAAF与ASPAAF诱导的肠损伤比较的实验研究 [J]. 中国普外基础与临床杂志, 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, 崔晓雨, 董良广, 等. 大鼠肠道缺血/再灌注时肠淋巴干结扎对肠道屏障的影响 [J]. 中国临床营养杂志, 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. 王兴鹏, 王冰娴, 吴恺, 等. 细胞凋亡在急性坏死型胰腺炎早期肠黏膜上皮细胞死亡中的作用 [J]. 中华消化杂志, 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, 吕艺, 付小兵, 等. 二胺氧化酶在创伤后肠道损伤中变化及意义 [J]. 中国危重病急救医学, 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. 程礼, 王兴鹏, 汪佩文, 等. 保护肠屏障功能对重症急性胰腺炎患者预后的影响 [J]. 胃肠病学, 2005; 10(1)： 2426.
27. 中华医学会消化病学分会. 肠屏障功能障碍临床诊治建议 [J]. 中华消化杂志, 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. 陈宏, 贾建国, 李非, 等. 肠内营养对重症急性胰腺炎预后的影响 [J]. 中国临床营养杂志, 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. 余利坚，徐亮，姚晖，等. 肠内免疫营养和生态营养对创伤后大鼠肠屏障功能的影响 [J]. 中国普外基础与临床杂志, 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. 早期肠内营养在重症急性胰腺炎治疗中的应用 [J]. 中国普外基础与临床杂志， 2008; 15(8)： 567571.
40. 刘波, 乔颖欣, 周家驹. 泻下药和解表药的现代药理解释 [J]. 中国药学杂志, 2007; 42(6)： 422426.
41. 邓群, 黎沾良, 陈连荣, 等. 生长抑素减轻大鼠急性坏死性胰腺炎的肠屏障损害 [J]. 中华普通外科杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advancement in Intestinal Barrier Dysfunction of Severe Acute Pancreatitis

Abstract Full text Figures/Tables Video References Cited by

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