Vasoactive intestinal peptide promotes gut barrier function against severe acute pancreatitis

被引:35
作者
Lu Zhongkai [1 ]
Ye Jianxin [1 ]
Chen Weichang [1 ]
机构
[1] Soochow Univ, Dept Gastroenterol, Affiliated Hosp 1, Suzhou 215006, Jiangsu, Peoples R China
关键词
Vasoactive intestinal peptide; Severe acute pancreatitis; Gut barrier; Inflammation; NF-KAPPA-B; BACTERIAL TRANSLOCATION; ORGAN FAILURE; PERMEABILITY; RATS; DYSFUNCTION; ACTIVATION; DEXAMETHASONE; MECHANISMS; CYTOKINES;
D O I
10.1007/s11033-011-1129-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To explore the influence of vasoactive intestinal peptide (VIP) on the gut barrier function in severe acute pancreatitis (SAP). Fifty four SD rats were randomly divided into three groups: sham operated (SO) group, SAP group and VIP intervention group. Each group was further divided into three time points: 1, 6 and 12 h after operation with 6 rats for each treatment point. SAP models were induced by retrograde injection of 4% sodium taurocholate into the bili-pancreatic duct. VIP intervention group was made by 5 nmol VIP intraperitoneal injection within 5 min after SAP model successfully obtained. The VIP in plasma and intestinal homogenate were detected with ELISA. The endotoxin in plasma of all groups was also tested. The expression levels of TLR4, TNF-alpha, IL-6, and IL-10 in gut mucosa were measured by RT-PCR. Meanwhile intestinal samples were harvested for pathological examination. Compared to SO group, the VIP in plasma and intestinal homogenate of SAP group were significantly decreased at 1 h after induction, and then gradually increased to beyond the level of SO group at 12 h. The endotoxin of SAP group was continually increased. The mRNA levels of TLR4, TNF-alpha, IL-6, and IL-10 were also increased with obvious pathological injuries in the intestine. In the VIP group, endotoxin in plasma was obviously decreased compared to SAP group. The expressions of TNF-alpha, IL-6 mRNA were suppressed while IL-10mRNA was increased. The intestinal pathological injuries were also markedly alleviated. These results suggested that VIP had protective effects on SAP gut barrier function through inhibiting intestinal mucosal inflammatory responses.
引用
收藏
页码:3557 / 3563
页数:7
相关论文
共 39 条
[1]   Role of the gut in the course of severe acute pancreatitis [J].
Ammori, BJ .
PANCREAS, 2003, 26 (02) :122-129
[2]   Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality [J].
Ammori, BJ ;
Leeder, PC ;
King, RFGJ ;
Barclay, GR ;
Martin, IG ;
Larvin, M ;
McMahon, MJ .
JOURNAL OF GASTROINTESTINAL SURGERY, 1999, 3 (03) :252-261
[3]   Intestinal Barrier Dysfunction in a Randomized Trial of a Specific Probiotic Composition in Acute Pancreatitis [J].
Besselink, Marc G. ;
van Santvoort, Hjalmar C. ;
Renooij, Willem ;
de Smet, Martin B. ;
Boermeester, Marja A. ;
Fischer, Kathelijn ;
Timmerman, Harro M. ;
Ali, Usama Ahmed ;
Cirkel, Geert A. ;
Bollen, Thomas L. ;
van Ramshorst, Bert ;
Schaapherder, Alexander F. ;
Witteman, Ben J. ;
Ploeg, Rutger J. ;
van Goor, Harry ;
van Laarhoven, Cornelis J. ;
Tan, Adriaan C. ;
Brink, Menno A. ;
van der Harst, Erwin ;
Wahab, Peter J. ;
van Eijck, Casper H. ;
Dejong, Cornelis H. ;
van Erpecum, Karel J. ;
Akkermans, Louis M. ;
Gooszen, Hein G. .
ANNALS OF SURGERY, 2009, 250 (05) :712-719
[4]   Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms [J].
Bruewer, M ;
Luegering, A ;
Kucharzik, T ;
Parkos, CA ;
Madara, JL ;
Hopkins, AM ;
Nusrat, A .
JOURNAL OF IMMUNOLOGY, 2003, 171 (11) :6164-6172
[5]   Signaling mechanisms of vasoactive intestinal peptide in inflammatory conditions [J].
Chorny, Alejo ;
Gonzalez-Rey, Elena ;
Varela, Niveves ;
Robledo, Gerna ;
Delgado, Mario .
REGULATORY PEPTIDES, 2006, 137 (1-2) :67-74
[6]   PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP [J].
CHRIVIA, JC ;
KWOK, RPS ;
LAMB, N ;
HAGIWARA, M ;
MONTMINY, MR ;
GOODMAN, RH .
NATURE, 1993, 365 (6449) :855-859
[7]   Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis [J].
Conlin, V. S. ;
Wu, X. ;
Nguyen, C. ;
Dai, C. ;
Vallance, B. A. ;
Buchan, A. M. J. ;
Boyer, L. ;
Jacobson, K. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2009, 297 (04) :G735-G750
[8]   Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis [J].
de Campos, Tercio ;
Deree, Jessica ;
Martins, Joilson O. ;
Loomis, William H. ;
Shenvi, Edna ;
Putnam, James G. ;
Coimbra, Raul .
PANCREAS, 2008, 37 (01) :42-49
[9]   Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases [J].
Delgado, M ;
Abad, C ;
Martinez, C ;
Juarranz, MG ;
Arranz, A ;
Gomariz, RP ;
Leceta, J .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2002, 80 (01) :16-24
[10]   Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit nuclear factor-κB-dependent gene activation at multiple levels in the human monocytic cell line THP-1 [J].
Delgado, M ;
Ganea, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (01) :369-380