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Journal of Zhejiang University SCIENCE B 2007 Vol.8 No.12 P.888~895


Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Author(s):  Zhang Xi-ping, Zhang Jie, Song Qiao-ling, Chen Han-qin

Affiliation(s):  Department of General Surgery, Hangzhou First People’ more

Corresponding email(s):   zxp99688@vip.163.com

Key Words:  Acute pancreatitis (AP), Intestinal mucosa barrier, Microcirculation disturbance, Apoptosis, Inflammatory mediators

Zhang Xi-ping, Zhang Jie, Song Qiao-ling, Chen Han-qin. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier[J]. Journal of Zhejiang University Science B, 2007, 8(12): 888~895.

@article{title="Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier",
author="Zhang Xi-ping, Zhang Jie, Song Qiao-ling, Chen Han-qin",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier
%A Zhang Xi-ping
%A Zhang Jie
%A Song Qiao-ling
%A Chen Han-qin
%J Journal of Zhejiang University SCIENCE B
%V 8
%N 12
%P 888~895
%@ 1673-1581
%D 2007
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2007.B0888

T1 - Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier
A1 - Zhang Xi-ping
A1 - Zhang Jie
A1 - Song Qiao-ling
A1 - Chen Han-qin
J0 - Journal of Zhejiang University Science B
VL - 8
IS - 12
SP - 888
EP - 895
%@ 1673-1581
Y1 - 2007
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2007.B0888

acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Al-Omran, M., Groof, A., Wilke, D., 2003. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst. Rev., 1:CD002837.

[2] Ammori, B.J., Fitzgerald, P., Hawkey, P., McMahon, M.J., 2003. The early increase in intestinal permeability and systemic endotoxin exposure in patients with severe acute pancreatitis is not associated with systemic bacterial translocation: molecular investigation of microbial DNA in the blood. Pancreas, 26(1):18-22.

[3] Antonelli, A., Bianchi, M., Crinelli, R., Gentilini, L., Magnani, M., 2001. Modulation of ICAM-1 expression in ECV304 cells by macrophage-released cytokines. Blood Cells Mol. Dis., 27(6):978-991.

[4] Avgerinos, C., Delis, S., Rizos, S., Dervenis, C., 2003. Nutritional support in acute pancreatitis. Dig. Dis., 21(3):214-219.

[5] Bzowska, M., Guzik, K., Barczyk, K., Ernst, M., Flad, H.D., Pryjma, J., 2002. Increased IL-10 production during spontaneous apoptosis of monocytes. Eur. J. Immunol., 32(7):2011-2020.

[6] Carnovale, A., Rabitti, P.G., Manes, G., Esposito, P., Pacelli, L., Uomo, G., 2005. Mortality in acute pancreatitis: is it an early or a late event? JOP, 6(5):438-444.

[7] Cheng, W.X., Jin, L.J., 1998. Study on apoptosis in multiple organs at early stage of rat intestinal ischemia-reperfusion injury. Chin. J. Traumatol., 14(6):381-383 (in Chinese).

[8] Closa, D., Folch-Puy, E., 2004. Oxygen free radicals and the systemic inflammatory response. IUBMB Life, 56(4):185-191.

[9] de las Heras, G., Forcelledo, J.L., Gutierrez, J.M., Calvo, J., Obaya, S., Fernandez, F., Mayorga, M., Aguero, J., Pons, R.F., 2000. Selective intestinal bacterial decontamination in experimental acute pancreatitis. Gastroenterol. Hepatol., 23(10):461-465.

[10] Dunger, A., Augstein, P., Schmidt, S., Fischer, U., 1996. Identification of interleukin 1-induced apoptosis in rat islets using in situ specific labelling of fragmented DNA. J. Autoimmun., 9(3):309-313.

[11] Exner, R., Weingartmann, G., Eliasen, M.M., Gerner, C., Spittler, A., Roth, E., Oehler, R., 2002. Glutamine deficiency renders human monocytic cells more susceptible to specific apoptosis triggers. Surgery, 131(1):75-80.

[12] Foitzik, T., Kruschewski, M., Kroesen, A.J., Hotz, H.G., Eibl, G., Buhr, H.J., 1999. Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier. Int. J. Colorectal Dis., 14(3):143-149.

[13] Foitzik, T., Eibl, G., Hotz, H.G., Faulhaber, J., Kirchengast, M., Buhr, H.J., 2000. Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates. Surgery, 128(3):399-407.

[14] Foitzik, T., Eibl, G., Hotz, B., Hotz, H., Kahrau, S., Kasten, C., Schneider, P., Buhr, H.J., 2002. Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications. Dig. Dis. Sci., 47(1):130-138.

[15] Fukuyama, K., Iwakiri, R., Noda, T., Kojima, M., Utsumi, H., Tsunada, S., Sakata, H., Ootani, A., Fujimoto, K., 2001. Apoptosis induced by ischemia-reperfusion and fasting in gastric mucosa compared to small intestinal mucosa in rats. Dig. Dis. Sci., 46(3):545-549.

[16] Furuya, T., Soeno, T., Komatsu, M., 2004. Strategy for bacterial translocation in acute pancreatitis. Nippon Shokakibyo Gakkai Zasshi, 101(5):502-509.

[17] Garside, P., Millington, O., Smith, K.M., 2004. The anatomy of mucosal immune responses. Ann. N. Y. Acad. Sci., 1029(1):9-15.

[18] Ginis, I., Jaiswal, R., Klimanis, D., Liu, J., Greenspon, J., Hallenbeck, J.M., 2002. TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. J. Cereb. Blood Flow Metab., 22(2):142-152.

[19] Gloor, B., Muller, C.A., Worni, M., Stahel, P.F., Redaelli, C., Uhl, W., Buchler, M.W., 2001. Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organisms. Arch. Surg., 136(5):592-596.

[20] Grady, E.F., Yoshimi, S.K., Maa, J., Valeroso, D., Vartanian, R.K., Rahim, S., Kim, E.H., Gerard, C., Gerard, N., Bunnett, N.W., et al., 2000. Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. Br. J. Pharmacol., 130(3):505-512.

[21] Harari, Y., Weisbrodt, N.W., Moody, F.G., 2000. Ileal mucosal response to bacterial toxin challenge. J. Trauma, 49(2):306-313.

[22] Hotz, H.G., Foitzik, T., Rohweder, J., Schulzke, J.D., Fromm, M., Runkel, N.S., Buhr, H.J., 1998. Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications. J. Gastrointest. Surg., 2(6):518-525.

[23] Ikeda, H., Suzuki, Y., Suzuki, M., Koike, M., Tamura, J., Tong, J., Nomura, M., Itoh, G., 1998. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut, 42(4):530-537.

[24] Izumi, T., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Hamanaka, I., Takahashi, N., Kawakami, R., Li, Y., Takemura, G., et al., 2001. Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury. J. Clin. Invest., 108(2):203-213.

[25] Jaworek, J., Jachimczak, B., Tomaszewska, R., Konturek, P.C., Pawlik, W.W., Sendur, R., Hahn, E.G., Stachura, J., Konturek, S.J., 2000. Protective action of lipopolysaccharidesin rat caerulein-induced pancreatitis: role of nitric oxide. Digestion, 62(1):1-13.

[26] Ji, L., Yuan, Y.Z., Xu, J.Y., 2000. NF-κB and acute pancreatitis. Foreign Medicine Internal Medicine, 27(9):396-398 (in Chinese).

[27] Jones, B.A., Gores, G.J., 1997. Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine. Am. J. Physiol., 273(6):G1174-G1188.

[28] Kazantsev, G.B., Hecht, D.W., Rao, R., Fedorak, I.J., Gattuso, P., Thompson, K., Djuricin, G., Prinz, R.A., 1994. Plasmid labeling confirms bacterial translocation in pancreatitis. Am. J. Surg., 167(1):201-206.

[29] Kiyono, H., Kweon, M.N., Hiroi, T., Takahashi, I., 2001. The mucosal immune system: from specialized immune defense to inflammation and allergy. Acta Odontol. Scand., 59(3):145-153.

[30] Lakshminarayanan, V., Lewallen, M., Frangogiannis, N.G., Evans, A.J., Wedin, K.E., Michael, L.H., Entman, M.L., 2001. Reactive oxygen intermediates induce monocyte chemotactic protein-1 in vascular endothelium after brief ischemia. Am. J. Pathol., 159(4):1301-1311.

[31] Li, Z.L., 1998. Intestinal bacteria translocation and severe surgical cases. Chin. J. Surg., 36(A00):11-12 (in Chinese).

[32] Liu, J., Qiu, Z.J., Peng, Z.H., Zhong, F.Q., 2001. Secondary infection of acute severe pancreatitis in rats with enteral nutrition decrease. Parenter. Enteral Nutr., 8(4):224-226 (in Chinese).

[33] Liu, S.J., McHowat, J., 1998. Stimulation of different phospholipase A2 isoforms by TNF-alpha and IL-1beta in adult rat ventricular myocytes. Am. J. Physiol., 275(4): H1462-H1472.

[34] Liu, Z.H., Striker, G.E., Stetler-Stevenson, M., Fukushima, P., Patel, A., Striker, L.J., 1996. TNF-alpha and IL-1 alpha induce mannose receptors and apoptosis in glomerular mesangial but not endothelial cells. Am. J. Physiol., 270(6):C1595-C601.

[35] Maa, J., Grady, E.F., Yoshimi, S.K., Drasin, T.E., Kim, E.H., Hutter, M.M., Bunnett, N.W., Kirkwood, K.S., 2000. Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice. Surgery, 128(2):232-239.

[36] Marik, P.E., Zaloga, G.P., 2004. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ, 328(7453):1407.

[37] Moine, P., McIntyre, R., Schwartz, M.D., Kaneko, D., Shenkar, R., Le, T.Y., Moore, E.E., Abraham, E., 2000. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome. Shock, 13(2):85-91.

[38] Mole, D.J., Taylor, M.A., McFerran, N.V., Diamond, T., 2005. The isolated perfused liver response to a ‘second hit’ of portal endotoxin during severe acute pancreatitis. Pancreatology, 5(4-5):475-485.

[39] Neurath, M.F., Becker, C., Barbulescu, K., 1998. Role of NF-κB in immune and inflammatory responses in the gut. Gut, 43(6):856-860.

[40] Nordback, I.H., Cameron, J.L., 1993. The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preperation. Surgery, 113(1):90-97.

[41] Omoya, T., Shimizu, I., Zhou, Y., Okamura, Y., Inoue, H., Lu, G., Itonaga, M., Honda, H., Nomura, M., Ito, S., 2001. Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress. Liver Int., 21(3):183-191.

[42] Penalva, J.C., Martinez, J., Laveda, R., Esteban, A., Munoz, C., Saez, J., Such, J., Navarro, S., Feu, F., Sanchez-Paya, J., Perez-Mateo, M., 2004. A study of intestinal perme ability in relation to the inflammatory response and plasma endocab IgM levels in patients with acute pancreatitis. J. Clin. Gastroenterol., 38(6):512-517.

[43] Raab, S., Leiser, R., Kemmer, H., Claus, R., 1998. Effects of energy and purines in the diet on proliferation, differentiation, and apoptosis in the small intestine of the pig. Metabolism, 47(9):1105-1111.

[44] Rahman, S.H., Ammori, B.J., Holmfield, J., Larvin, M., McMahon, M.J., 2003. Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. J. Gastrointest. Surg., 7(1):26-35.

[45] Schmidt, J., Rattner, D.W., Lewandrowski, K., Compton, C.C., Mandavilli, V., Knoefel, W.T., Warshaw, A.L., 1992. A better model of acute pancreatitis for evaluating therapy. Ann. Surg., 215(1):44-56.

[46] Schwarz, M., Thomsen, J., Meyer, H., Buchler, M.W., Beger, H.G., 2000. Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats. Surgery, 127(4):427-432.

[47] Shames, B.D., Barton, H.H., Reznikov, L.L., Cairns, C.B., Banerjee, A., Harken, A.H., Meng, X., 2002. Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium. Shock, 17(2):114-119.

[48] Su, B., 1998. Study progress on apoptosis and ischemia-reperfusion injury. Foreign Medicine Surgery, 25(5):325-327 (in Chinese).

[49] Sunamura, M., Yamauchi, J., Shibuya, K., Chen, H.M., Ding, L., Takeda, K., Kobari, M., Matsuno, S., 1998. Pancreatic microcirculation in acute pancreatitis. J. Hepatobiliary Pancreat. Surg., 5(1):62-68.

[50] Swank, G.M., Lu, Q., Xu, D.Z., Michalsky, M., Deitch, E.A., 1998. Effect of acute-phase and heat-shock stress on apoptosis in intestinal epithelial cells (Caco-2). Crit. Care Med., 26(7):1213-1217.

[51] Takahashi, Y., Fukushima, J., Fukusato, T., Shiga, J., Tanaka, F., Imamura, T., Fukayama, M., Inoue, T., Shimizu, S., Mori, S., 2005. Prevalence of ischemic enterocolitis in patients with acute pancreatitis. J. Gastroenterol., 40(8):827-832.

[52] Theuer, J., Dechend, R., Muller, D.N., Park, J.K., Fiebeler, A., Barta, P., Ganten, D., Haller, H., Dietz, R., Luft, F.C., 2002. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats. BMC Cardiovasc. Disord., 2(1):3.

[53] Valen, G., Yan, Z.Q., Hansson, G.K., 2001. Nuclear factor kappa-B and the heart. J. Am. Coll. Cardiol., 38(2):307-314.

[54] Wang, X.P., Wang, B.X., Wu, K., Xu, X.F., 2001a. Role of apoptosis in death of intestinal mucosa epithelial cell at early stage of acute necrotic pancreatitis. Chin. J. Dig., 21(5):267-270 (in Chinese).

[55] Wang, X.P., Wu, K., Wang, B.X., Xu, X.F., Xu, M., Gong, Z.H., 2001b. Therapeutic effect of glutamine on intestinal failure of rats with acute necrotic pancreatitis. Chin. J. Intern. Med., 40(12):815-818 (in Chinese).

[56] Wang, X.P., Wang, B.X., Xu, X.F., Xie, C.G., Wu, K., XU, M., 2001c. CD44 mRNA expression of intestinal mucosa of rats with acute necrotic pancreatitis and role of somatropin. Chin. J. Exp. Surg., 18(4):305-306 (in Chinese).

[57] Wang, X.P., Wang, B.X., Wu, K., Xu, X.F., Xie, C.G., Xu, M., 2003. Excessive cytokine expression mediated by NF-κB of intestinal mucosa and role of somatropin in acute necrotic pancreatitis. Chin. J. Hepatobiliary Surg., 9(1):45-49 (in Chinese).

[58] Wang, Z., Castresana, M.R., Detmer, K., Newman, W.H., 2002. An IkappaB-alpha mutant inhibits cytokine gene expression and proliferation in human vascular smooth muscle cells. J. Surg. Res., 102(2):198-206.

[59] Wang, Z.F., Pang, C.E., Liu, S.G., Liang, G.G., Zhang, M., 2000. Hemorheological change of acute necrotic pancreatitis and its significance. Chin. J. Gen. Surg., 9(3):225 (in Chinese).

[60] Wright, G., Singh, I.S., Hasday, J.D., Farrance, I.K., Hall, G., Cross, A.S., Rogers, T.B., 2002. Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor necrosis factor-alpha expression. Am. J. Physiol. Heart Circ. Physiol., 282(3):872-879.

[61] Wu, C.T., Li, Z.L., 1999. Role of nitrogen monoxidum and endothelin in intestinal injury of acute necrotic pancreatitis. Chin. J. Gen. Surg., 8(3):210-212 (in Chinese).

[62] Wu, Z.J., Zhang, Y.D., Lei, Z.M., Xu, S.H., 2003. Dynamic determination of concentration of TNF-α, IL-6 in peripheral blood of rats with acute necrotic pancreatitis and its significance. China J. Mod. Med., 13(4):23-25 (in Chinese).

[63] Yang, F.R., Lin, X.Z., 2002. Study progress on intestinal ischemical reperfusion injury. Chin. J. Integr. Tradit. Western Med., 8(4):319-321 (in Chinese).

[64] Yang, Y.J., Gao, N.R., 2005. Influence of endogenous nitrogen monoxidum on permeability of intestinal mucosa of rats with acute necrotic pancreatitis. World Chin. J. Digestol., 13(3):389-391 (in Chinese).

[65] Yin, J.B., Xiao, J.M., Wang, Y.Q., Wang, S.C., 2005. Acute pancreatitis and intestinal barrier injury, bacteria translocation and endotoxemia. Chin. J. Coal Ind. Med., 8(4):317-320 (in Chinese).

[66] Zhang, J.X., Qu, J.G., Cheng, G.Z., Li, L., Wang, X.Q., 2003. Changes of intestinal blood flow and phospholipase A2, interleukin-1β in serum of rats with acute necrotic pancreatitis. Basic Med. Sci. Clin., 23(5):556-558 (in Chinese).

[67] Zheng, T.B., Shi, X., Gao, N.R., Huo, M.D., Hu, H.L., Yang, Y.J., 2002. Expression of NK-1R and NK-2R in colon during acute necrotic pancreatitis. J. Pract. Med., 18(12):1272-1274 (in Chinese).

[68] Zou, S., Shao, H., Huang, D.R., Tian, F.Z., Yin, Z.L., Li, X.J., Wang, T., Gao, X.M., 2001. Experimental study on protecting mechanism of adenosine in intestinal barrier function during acute hemorrhagic necrotic pancreatitis. Chin. J. Gen. Surg., 10(4):305-308 (in Chinese).

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