选择性消化道去污对大鼠重症胰腺炎细菌移位的影响
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摘要
目的：探讨选择性消化道去污在大鼠重症急性胰腺炎模型中对细菌移位及炎症反应的影响。
方法：48只SD大鼠随机分为正常对照组(norm组)、假手术组(sham组)、重症急性胰腺炎组(SAP组)、选择性消化道去污+重症急性胰腺炎组(SDD组)。采用胰胆管逆行注射4％牛磺胆酸钠的方法，建立SAP大鼠模型；SDD组术前用三联抗生素灌胃三天(庆大霉素2万U+多粘菌素10万U+制霉菌素10万U，Q8h)。24h后处死，观察腹腔大致变化并对胰腺组织做病理学评分；对肠道细菌进行计数；取胰腺和胰外组织肺、肝、脾、肾标本做细菌培养；检测胰腺组织髓过氧化物酶(MPO)及门静脉内毒素(LPS)和体循环血浆肿瘤坏死因子(TNFα)的表达水平。
结果：SAP组和SDD组在诱导SAP后，出现明显的细菌移位，肠道细菌计数和MPO、LPS及TNFα浓度比norm组和sham组均显著性升高；但SDD组各脏器细菌培养阳性率和肠道细菌计数及MPO、LPS、TNFα浓度与SAP组比较均有明显下降；前者的胰腺组织病理学评分也有所降低。
结论：在SAP大鼠模型中选择性消化道去污清除肠道细菌可减少肠源性感染，从而减轻炎症反应。
Objective: To explore the effect of selective digestive decontamination (SDD) to decrease bacterial translocation and relieve inflatmmatory response in sever acute pancreatitis (SAP) in rats.
Methods: The Sprague-Dawley rats were divided randomly into norm group, sham-operated group, SAP group, SDD group. SAP was induced by intraductal injection of 4% sodium taurocholate. SDD group underwent bacterial decontamination through the administration of Gentamycin, Polymyxin and Nystatin during the 3 days prior to SAP induction. 24 hours after SAP induction, laparotomy was performed and samples for the bacterial culture of pancreas, lung, liver, spleen and kidney was obtained. Intestinal bacteria was counted. A point scoring system of histologicalal features was used to evaluate the severity of pancreatitis. The levels of blood endotoxin in portal vein and plasma TNF alpha in venae cavae were measured. Pancreatic myeloperoxidase (MPO) were detected at the same time.
Results : In the SAP and SDD group, there was significant pancreatic and extrapancreatic infection 24 hours after induction of pancreatitis, counting of intestinal bacteria, plasma concentrations of endotoxin and TNF alpha were significantly higher than in norm group and sham-operated group controls. Compared with SAP group, all of above-mentioned indexes were decreased in SDD group.
Conclusions The incidence of bacterial translocation and the severity of SAP can decreased by SDD prior to SAP induction.
方法：48只SD大鼠随机分为正常对照组(norm组)、假手术组(sham组)、重症急性胰腺炎组(SAP组)、选择性消化道去污+重症急性胰腺炎组(SDD组)。采用胰胆管逆行注射4％牛磺胆酸钠的方法，建立SAP大鼠模型；SDD组术前用三联抗生素灌胃三天(庆大霉素2万U+多粘菌素10万U+制霉菌素10万U，Q8h)。24h后处死，观察腹腔大致变化并对胰腺组织做病理学评分；对肠道细菌进行计数；取胰腺和胰外组织肺、肝、脾、肾标本做细菌培养；检测胰腺组织髓过氧化物酶(MPO)及门静脉内毒素(LPS)和体循环血浆肿瘤坏死因子(TNFα)的表达水平。
结果：SAP组和SDD组在诱导SAP后，出现明显的细菌移位，肠道细菌计数和MPO、LPS及TNFα浓度比norm组和sham组均显著性升高；但SDD组各脏器细菌培养阳性率和肠道细菌计数及MPO、LPS、TNFα浓度与SAP组比较均有明显下降；前者的胰腺组织病理学评分也有所降低。
结论：在SAP大鼠模型中选择性消化道去污清除肠道细菌可减少肠源性感染，从而减轻炎症反应。
Objective: To explore the effect of selective digestive decontamination (SDD) to decrease bacterial translocation and relieve inflatmmatory response in sever acute pancreatitis (SAP) in rats.
Methods: The Sprague-Dawley rats were divided randomly into norm group, sham-operated group, SAP group, SDD group. SAP was induced by intraductal injection of 4% sodium taurocholate. SDD group underwent bacterial decontamination through the administration of Gentamycin, Polymyxin and Nystatin during the 3 days prior to SAP induction. 24 hours after SAP induction, laparotomy was performed and samples for the bacterial culture of pancreas, lung, liver, spleen and kidney was obtained. Intestinal bacteria was counted. A point scoring system of histologicalal features was used to evaluate the severity of pancreatitis. The levels of blood endotoxin in portal vein and plasma TNF alpha in venae cavae were measured. Pancreatic myeloperoxidase (MPO) were detected at the same time.
Results : In the SAP and SDD group, there was significant pancreatic and extrapancreatic infection 24 hours after induction of pancreatitis, counting of intestinal bacteria, plasma concentrations of endotoxin and TNF alpha were significantly higher than in norm group and sham-operated group controls. Compared with SAP group, all of above-mentioned indexes were decreased in SDD group.
Conclusions The incidence of bacterial translocation and the severity of SAP can decreased by SDD prior to SAP induction.
引文
1. Hall J, Heel KA, Papadimitriou JM, et al. The pathobiology of peritonitis. Gastroenterology, 1998; 114:185-96.
2. Iseberg RR, Barnes P. Border patrols and secret passageways across the intestinal epithelium. Trends Microbiol, 2000; 8:291-293
3. Lemaire LC, Lanschot JJ, Stoutenbeck CP, et al. Bacterial translocation in multiple organ failure: cause or epiphenomenon still unproven. Br J Surg, 1997; 84: 340-350.
4. Mutinga M, Rosenbluth A, Tenner SM, et al. Does mortality occur early or late in acute pancreatitis. Int J Pancreatol, 2000; 28:91-95
5. Nettelbladt CG, Katouli M, Bark T, et al. Evidence of Bacterial Translocation in Fatal Hemorrhagic Pancreatitis. Trauma, 2000; 48(2): 314-316
6. Foitzik T. The enteral factor in pancreatic infection. Pancreatology, 2001; 1:217-223.
7. Yao V, Cooper D, McCauley R, et al. Bacterial translocation in a non-lethal rat model of peritonitis. Colorectal Disease, 2001; 3(5): 338-340
8. Beger HG. Rau B, Mayer J. et al. Natural course of acute pancreatitis, World J Surg, 1997; 21:130-135
9. Widdison AL, Karanjia ND, Reber HA. Routes of spread of pathogens into the pancreas in a feline model of acute pancreatitis. Gut, 1994; 35:1306-1310.
10. Wang XD, Andersson R, Soltesz V, et al. Gut orign Sepsis, macrophage function and oxygen extraction associated with acute pancreatitis in the rat. World J surg, 1996; 20: 299-308
11. Schmid SW, Uhl W, Friess H, et al. The role of infection in acute pancreatitis. Gut, 1999; 45(2): 311-316
12. Berg RD. Garlingtor AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph modes and other organs in a gnotobiotic mouse model. Infect Immun, 1979, 23:403-411
13. Alexander JW, Boyce ST, Babcock GF, et al. The process of microbial translocation.
Ann Surg, 1990, 212:496-512
14. Lichtman, Steven M. Bacterial translocation in Humans. Journal of Gastroenterology and nutrition, 2001; 33(1):1-10
15. Erwin PJ, Lewis H, Dolan S, et al. Lipopolysaccharide blinding protein in acute pancreatitis. Crit Care Med, 2000; 28:104-109.
16．王兴鹏，王冰娴，徐选福等，肠源性内毒素血症促使水肿型胰腺炎向坏死型胰腺炎转化．中华消化杂志，2001；2，21(1)：71-74
17．陈建，罗向东，杨宗城．内毒素激活效应细胞的分子机制．第三军医大学学报，1999；11(21)：866-868
18. Lampel M, Kem HF. Acute interstitial pancreatitis in the rat in duced by excessive doses of a pancreatic secretagogue. VirchowsArch, 1977; 373: 97-117
19. Arendt T, Wendt M, Olszewski M, et al. Cerulein-induced acute pancreatitis in rats—does bacterial translocation occur via a transperitoneal pathway. Pancreas, 1997, 15(3): 291-296
20. Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor is an endogenous pyrogen and induces production of interleukinl. J Exp Med, 1986, 163: 1433-1450.
21. Runkel N, Moody FG, Smith GS, et al. The role of the gut in the development of sepsis in acute pancreatitis. J Surg Res, 1991; 51:18-23
22. Matsumoto T, Tateda K, Miyazaki S, et al. Paradoxical synergistic effects of tumour necrosis factor and interleukin 1 in murine gut-derived sepsis with Pseudomonas aeruginosa. Cytokine, 1999; 11(5): 366-372
23. Aho H, Koskensalo S, Nevalainen T, et al. Experimental pancreatitis in the rat: sodium taurocholate induced acute haemorrhagic pancteatitis. Scand J Gastroenterol, 1980; 15:411-416.
24．王单松，靳大勇，吴肇汉等，急性出血坏死型胰腺炎大鼠模型，上海实验动物科学．2002；3，22(1)：23-25
25. Krueger W, Unertl K. Selective decontamination of the digestive tract. Curr Opin Crit Care, 2002; 8(2): 139-144
26. Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg, 1999; 134(2):170-176
27. Parra ML, Arias RS, Lopez MA, et al. Effect of selective digestive decontamination on the nosocomial infection and multiresistant microorganisms incidence in critically ill patients. Medicina clinica, 2002; 118(10): 361-364
28. Schwarz M, Thomsen J, Meyer H, et al. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery, 2000; 127(4): 427-432
29．孙敬方主编．《动物实验方法学》(第一版)，人民卫生出版社，2001；254-256
30. Rongione AJ, Kusske AM, Ashley SW, et al. Interleukine-10 reduce the severty of sever acute pancreatitis in rat. Gastroenterology, 1997; 112:960-967
31. Vander WD, Berghnisde JM, Lekervander W. Colonization resistantance of the digestive tract in conventional and antibiotic treated mice. J Hyg, 1971; 69:406
32. Vander WD. History of recognition and measurement of colonization resistance of the digestive tract as an introduction to selective gastrointestional decontamination. Epidemol Infect, 1992; 109:315
33. Vollaard EJ, Clasener H, Colonization resistance. Antimicrob Agents Chemother, 1994; 38:409
34. Schwarz M, Thomsen J, Meyer H, et al. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery, 2000; 127(4): 427-432
35. Lingnau W, Berger J, Javoesky F, et al. Selective intestinal decontamination in multiple trauma patients: propective controlled trial. J Trauma, 1997; 42:687-694
36. Wu CT, Li ZL, Xiong DX. Relationship between enteric microecologic dysbiosis and bacterial translocation in acute necrotizing pancreatitis. World J Gastroentero, 1998; 4(3): 242-245
37. Berg RD. Bacterial translocation from the gastrointestinal tract. Adv Exp Med Biol, 1999; 73:11-30
38. Rahman SH, James AM, Ammori BJ, et al. Ischaemia-reperfusion injury, gut macromolecular permeability and severe acute pancreatitis. Br J Surg, 2002; 89(1): 34
39. Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J Gastrointest Surg 2003; 7(1):26-35
40. Foitzik T. The enteral factor in pancreatic infection. Pancreatology, 2001; 1:217-223
41. Kazez A, Saglam M, Doymaz MZ, et al. Detection of bacterial translocation during intestinal distension in rats using the polymerase chain reaction. Pediatr Surg Int, 2001; 17(8): 624-627
42. Saidakhmedova ZT. Immunomodulating activity of thymogen in acute pancreatitis. Vopr Pitan, 2000; 69(6): 35-36
43. Kylanpaa ML, Takala A, Kemppainen E, et al. Cellular markers of systemic inflammation and immune suppression in patients with organ failure due to severe acute pancreatitis. Scand J Gastroenterol, 2001; 36(10): 1100 -1107
44. Chavez AM, Menconi MJ, Hodin RA, et al. Cytokine-induced intestinal ephithelial hyperpermeability: Role of nitric oxide. Crit Care Med, 1999; 25:2246-2251
45. Wig JD, Kochhar R, Ray JD, et al. Endotoxemia Predicts outcome in acute pancreatitis. J Clin Gastroenterol, 1998; 26:121-124.
46. Jun Y, Kazuhiko S, Makoto S, et al. Cytokine modulation in acute pancreatitis. J Hepatobiliary Pancreat Surg 2001; 8:195-203
47. Mayer J, Rau B, Gansauge F, et al. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut, 2000, 47(4): 546-552
48. O'Loughlin E, Winter M, Shun A, et al. Structural and functional adaptation following jejunal resection in rabbits: effect of epidermal growth factor. Gasteroenterology, 1994; 107(1): 87-93
49. Yamauchi J, Shibuya K, Sunamura M, et al. Cytokine modulation in acute pancreatitis. Journal of hepato-biliary-pancreatic surgery, 2001, 8:195-203
2. Iseberg RR, Barnes P. Border patrols and secret passageways across the intestinal epithelium. Trends Microbiol, 2000; 8:291-293
3. Lemaire LC, Lanschot JJ, Stoutenbeck CP, et al. Bacterial translocation in multiple organ failure: cause or epiphenomenon still unproven. Br J Surg, 1997; 84: 340-350.
4. Mutinga M, Rosenbluth A, Tenner SM, et al. Does mortality occur early or late in acute pancreatitis. Int J Pancreatol, 2000; 28:91-95
5. Nettelbladt CG, Katouli M, Bark T, et al. Evidence of Bacterial Translocation in Fatal Hemorrhagic Pancreatitis. Trauma, 2000; 48(2): 314-316
6. Foitzik T. The enteral factor in pancreatic infection. Pancreatology, 2001; 1:217-223.
7. Yao V, Cooper D, McCauley R, et al. Bacterial translocation in a non-lethal rat model of peritonitis. Colorectal Disease, 2001; 3(5): 338-340
8. Beger HG. Rau B, Mayer J. et al. Natural course of acute pancreatitis, World J Surg, 1997; 21:130-135
9. Widdison AL, Karanjia ND, Reber HA. Routes of spread of pathogens into the pancreas in a feline model of acute pancreatitis. Gut, 1994; 35:1306-1310.
10. Wang XD, Andersson R, Soltesz V, et al. Gut orign Sepsis, macrophage function and oxygen extraction associated with acute pancreatitis in the rat. World J surg, 1996; 20: 299-308
11. Schmid SW, Uhl W, Friess H, et al. The role of infection in acute pancreatitis. Gut, 1999; 45(2): 311-316
12. Berg RD. Garlingtor AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph modes and other organs in a gnotobiotic mouse model. Infect Immun, 1979, 23:403-411
13. Alexander JW, Boyce ST, Babcock GF, et al. The process of microbial translocation.
Ann Surg, 1990, 212:496-512
14. Lichtman, Steven M. Bacterial translocation in Humans. Journal of Gastroenterology and nutrition, 2001; 33(1):1-10
15. Erwin PJ, Lewis H, Dolan S, et al. Lipopolysaccharide blinding protein in acute pancreatitis. Crit Care Med, 2000; 28:104-109.
16．王兴鹏，王冰娴，徐选福等，肠源性内毒素血症促使水肿型胰腺炎向坏死型胰腺炎转化．中华消化杂志，2001；2，21(1)：71-74
17．陈建，罗向东，杨宗城．内毒素激活效应细胞的分子机制．第三军医大学学报，1999；11(21)：866-868
18. Lampel M, Kem HF. Acute interstitial pancreatitis in the rat in duced by excessive doses of a pancreatic secretagogue. VirchowsArch, 1977; 373: 97-117
19. Arendt T, Wendt M, Olszewski M, et al. Cerulein-induced acute pancreatitis in rats—does bacterial translocation occur via a transperitoneal pathway. Pancreas, 1997, 15(3): 291-296
20. Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor is an endogenous pyrogen and induces production of interleukinl. J Exp Med, 1986, 163: 1433-1450.
21. Runkel N, Moody FG, Smith GS, et al. The role of the gut in the development of sepsis in acute pancreatitis. J Surg Res, 1991; 51:18-23
22. Matsumoto T, Tateda K, Miyazaki S, et al. Paradoxical synergistic effects of tumour necrosis factor and interleukin 1 in murine gut-derived sepsis with Pseudomonas aeruginosa. Cytokine, 1999; 11(5): 366-372
23. Aho H, Koskensalo S, Nevalainen T, et al. Experimental pancreatitis in the rat: sodium taurocholate induced acute haemorrhagic pancteatitis. Scand J Gastroenterol, 1980; 15:411-416.
24．王单松，靳大勇，吴肇汉等，急性出血坏死型胰腺炎大鼠模型，上海实验动物科学．2002；3，22(1)：23-25
25. Krueger W, Unertl K. Selective decontamination of the digestive tract. Curr Opin Crit Care, 2002; 8(2): 139-144
26. Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg, 1999; 134(2):170-176
27. Parra ML, Arias RS, Lopez MA, et al. Effect of selective digestive decontamination on the nosocomial infection and multiresistant microorganisms incidence in critically ill patients. Medicina clinica, 2002; 118(10): 361-364
28. Schwarz M, Thomsen J, Meyer H, et al. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery, 2000; 127(4): 427-432
29．孙敬方主编．《动物实验方法学》(第一版)，人民卫生出版社，2001；254-256
30. Rongione AJ, Kusske AM, Ashley SW, et al. Interleukine-10 reduce the severty of sever acute pancreatitis in rat. Gastroenterology, 1997; 112:960-967
31. Vander WD, Berghnisde JM, Lekervander W. Colonization resistantance of the digestive tract in conventional and antibiotic treated mice. J Hyg, 1971; 69:406
32. Vander WD. History of recognition and measurement of colonization resistance of the digestive tract as an introduction to selective gastrointestional decontamination. Epidemol Infect, 1992; 109:315
33. Vollaard EJ, Clasener H, Colonization resistance. Antimicrob Agents Chemother, 1994; 38:409
34. Schwarz M, Thomsen J, Meyer H, et al. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery, 2000; 127(4): 427-432
35. Lingnau W, Berger J, Javoesky F, et al. Selective intestinal decontamination in multiple trauma patients: propective controlled trial. J Trauma, 1997; 42:687-694
36. Wu CT, Li ZL, Xiong DX. Relationship between enteric microecologic dysbiosis and bacterial translocation in acute necrotizing pancreatitis. World J Gastroentero, 1998; 4(3): 242-245
37. Berg RD. Bacterial translocation from the gastrointestinal tract. Adv Exp Med Biol, 1999; 73:11-30
38. Rahman SH, James AM, Ammori BJ, et al. Ischaemia-reperfusion injury, gut macromolecular permeability and severe acute pancreatitis. Br J Surg, 2002; 89(1): 34
39. Rahman SH, Ammori BJ, Holmfield J, et al. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J Gastrointest Surg 2003; 7(1):26-35
40. Foitzik T. The enteral factor in pancreatic infection. Pancreatology, 2001; 1:217-223
41. Kazez A, Saglam M, Doymaz MZ, et al. Detection of bacterial translocation during intestinal distension in rats using the polymerase chain reaction. Pediatr Surg Int, 2001; 17(8): 624-627
42. Saidakhmedova ZT. Immunomodulating activity of thymogen in acute pancreatitis. Vopr Pitan, 2000; 69(6): 35-36
43. Kylanpaa ML, Takala A, Kemppainen E, et al. Cellular markers of systemic inflammation and immune suppression in patients with organ failure due to severe acute pancreatitis. Scand J Gastroenterol, 2001; 36(10): 1100 -1107
44. Chavez AM, Menconi MJ, Hodin RA, et al. Cytokine-induced intestinal ephithelial hyperpermeability: Role of nitric oxide. Crit Care Med, 1999; 25:2246-2251
45. Wig JD, Kochhar R, Ray JD, et al. Endotoxemia Predicts outcome in acute pancreatitis. J Clin Gastroenterol, 1998; 26:121-124.
46. Jun Y, Kazuhiko S, Makoto S, et al. Cytokine modulation in acute pancreatitis. J Hepatobiliary Pancreat Surg 2001; 8:195-203
47. Mayer J, Rau B, Gansauge F, et al. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut, 2000, 47(4): 546-552
48. O'Loughlin E, Winter M, Shun A, et al. Structural and functional adaptation following jejunal resection in rabbits: effect of epidermal growth factor. Gasteroenterology, 1994; 107(1): 87-93
49. Yamauchi J, Shibuya K, Sunamura M, et al. Cytokine modulation in acute pancreatitis. Journal of hepato-biliary-pancreatic surgery, 2001, 8:195-203
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