Oxidative stress and apoptosis in gut barrier dysfunction of severe acute pancreatitis

( views:324, downloads:0 )
Author:
TIAN Rui(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
YU Kang-long(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
XU fei(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
WANG Rui-lan(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
XIE Hui(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
MENG Xiao-xiao(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
QIAN Yong-bing(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
JIN Wei(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
HU Jia-chang(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
ZHOU Zhi-gang(Department of ICU, First People's Hospital, Shanghai Jiaotong University, Shanghai 201620, china)
Journal Title:
Chinese Journal of Emergency Medicine
Issue:
Volume 21, Issue 10, 2012
DOI:
10.3760/cma.j.issn.1671-0282.2012.10.005
Key Word:
Systemic inflammatory response syndrome (SIRS); Inflammatory factors ; Ischemia-reperfusion injury ; Oxygen radicals; Oxidative stress; Apoptosis; Severe acute pancreatitis; Gut barrier dysfunction

Abstract: Objective By means of animal study,investigated the gut barrier function in severe acute pancreatitis ( SAP),and role of inflammatory factors releasing,gut mucosa oxidative stress,cell apoptosis in it.Methods The animal experiment was done in the animal center of first people' s hospital,shanghai jiaotong university.Twenty four BALB/c mice were randomized ( random number) divided into two groups with twelve mice each group.The SAP group,mice received six intraperitoneal injections of cerulein at 1-hour intervals, the dose was 50μg/kg, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide ( LPS from E.Coli) for the induction of severe acute pancreatitis.The control ( sham operation) group,the mice received intraperitoneal injection of 2 ml normal saline for six times at 1-hour intervals.All the animals of each group were averaged to two batches,4 h and 8h after being operated respectively,to be anesthetized and adopted blood and tissue specimen.Then we observed the pathological change of pancreas and gut,scored it.We measured the blood value of diamine oxidase ( DAO),amylase and tumor necrosis factor-α (TNF-α).We detected content of malondialdehyde (MDA),superoxide dismutase (SOD),glutathione (GSH) and activity of xanthine oxidase (XO) in gut mucosa.We detected the casepase-3 activity and cell apopotosis by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in gut mucosa,and conculated the apopotosis index (AI).Then using the PASW 18.0 software,we analyzed the data by anova and t-test,to make sure if the values were statistically different between the two groups and the mechanism of gut barrier dysfunction in panreatitis.Results At 4 h and 8 h after operation,the SAP-group-mice had significantly higher pancreas pathological score (P <0.01 ),blood amylase value ( P < 0.05 ),gut pathological score and blood DAO and TNF-α value ( P <0.01 ),compared with the contral-group-mice.The gut mucosa MDA content and XO activity of mice in SAP group were significantly higher than which in control group ( P < 0.01 ). The SAP-group-mice had significantly lower gut mucosa SOD content ( P < 0.01 ) and GSH content ( P < 0.05 ),compared with the contral-group-mice.The gut mucosa cells of mice in SAP group had significantly higher caspase-3 activity and apoptosis index than which in control group ( P < 0.01 ).Conclusions In severe acute pancreatitis,inflammatory factors such as TNF-αwere waterfall-style released,induced gut mucosa suffer from ischemia-reperfusion injury,then serious oxidative stress developed in mucosa and activated caspase-3 pathway,inducing gut mucosa cells apoptose seriously,which was an important mechanism of gut barrier dysfunction.

  • [1]Ahmed Z,Ammar D,Numan H,et al.Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome[J].Pancreas,2010,39 (7):1064-1069.
  • [2]O' Hara JR,Buret AG.Mechanisms of intestinal tight junctional disruption during infection[J]. Front Biosci,2008,13 (5):7008-7021.
  • [3]Chan YC,Leung PS.Animal models and recent advances in basic research[J].Pancreas,2007,34 (1):1-14.
  • [4]Schmidt J,Rattner DW,Lewandrowski K,et al.A better model of acute pancreatitis for evaluating therapy[J]. Ann Surg,1992,215 (1):44-56.
  • [5]黎友军,于燕,郝军,等.分光光度法测定血和小肠组织二胺氧化酶活性[J].氨基酸和生物资源,1996,18 (4):28-30.
  • [6]闻平.MTS/PMS比色法测定血清黄嘌呤氧化酶[J].陕西医学检验,2000,15 (1):10-11.
  • [7]Georgiou CD,Zervoudakis G,Tairis N,et al.β-Carotene production and its role in sclerotial differentiation of Sclerotium rolfsii[J].Fungal Genet Biol,2001,34 (1):11-20.
  • [8]Sakorafas GH,Lappas C,Mastoraki A,et al.Current trends in the management of infected necrotizing pancreatitis[J].Infect Disord Drug Targets,2010,10 (1):9-14.
  • [9]李小彦,王小波,刘秀峰,等.重症急性胰腺炎患者器官功能衰竭的患病率及其危险因素分析[J].中华急诊医学杂志,2011,20 (2):156-159.
  • [10]Sharma B,Srivastava S,Singh N,et al.Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis:a double-blind randomized controlled trial [J]. J Clin Gastroenterol,2011,45 (5):442-448.
  • [11]Zhang XP,Zhang J,Song QL,et al. Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier[J].J Zhejiang Univ Sci B,2007,8 (12):888-985.
  • [12]Kuefner MA,Schwelberger HG,Hahn EG,et al. Decreased histamine catabolism in the colonic mucosa of patients with colonic adenoma[J].Dig Dis Sci,2008,53 (2):436-442.
  • [13]殷凯,党胜春,张建新.髓系细胞触发受体-1对重症急性胰腺炎大鼠肠屏障功能的影响[J].中华急诊医学杂志,2011,20 (8):811-815.
  • [14]Zhou H,Gao J,Wu W,et al.Octreotide ameliorates intestinal dysmotility by interstitial cells of Cajal protection in a rat acute necrotizing pancreatitis model[J]. Pancreas,2011,40 (8):1226-1233.
  • [15]Fang J,Seki T,Qin H,et al.Tissue protective effect of xanthine oxidase inhibitor, polymer conjugate of (styrene-maleic acid copolymer) and (4-amino-6-hydroxypyrazolo [3,4-d]pyrimidine),on hepatic ischemia-reperfusion injury[J]. Exp Biol Med (Maywood),2010,235 (4):487-496.
  • [16]Abramov AY, Scorziello A, Duchen MR. Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation[J].J Neurosci,2007,27 (5):1129-1138.
  • [17]Mitsuoka H,Schmid-Schonbein GW.Mechanisms for blockade of in vivo activator production in the ischemic intestine and multiorgan failure[J].Shock,2000,24 (5):522-527.
  • [18]Ozkan E,Akyüz C,Dulundu E,et al. Protective effects of lycopene on cerulein-induced experimental acute pancreatitis in rats[J].J Surg Res,2012,176 (1):232-238.
  • [19]Bavita A,Shashi B,Navtej SB.Nitric oxide alleviates oxidative damage induced by high temperature stress in wheat[J].Indian J Exp Biol,2012,50 (5):372-378.
  • [20]Oruc EO,Sevgiler Y,Uner N.Tissue-specific oxidative stress responses in fish exposed to 2,4-D and azinphosmethyl[J].Comp Biochem Physiol C,2004,137 (1):43-51.
  • [21]Huppertz B,Frank HG. Kaufmann P. The apoptosis cascade morphological and immuno-histochemical methods for its visualization[J].Anat Embryol,2008,200 (3):1218.
  • [22]Yasuda T,Takeyama Y, Ueda T. Protective effect of caspase inhibitor on intestinal integrity in experimental severe acute pancreatitis[J].J Surg Res,2007,138 (23):300-307.
  • [23]George SK,Jiao Y,Bishop CE,et al.Oxidative stress is involved in age-dependent spermatogenic damage of lmmp21 mutant mice[J].Free Radic Biol Med,2012,52 (11-12):2223-2233.
  • [24]Susztak K, Raft AC, Sehiffer M, et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy[J]. Diabetes,2006,55 (1):225-233.
  • [25]Menini S,Amadio L,Oddi G,et al.Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress [J]. Diabetes,2006,55 (6):1642-1650.
  • [26]Lee YJ,Kang LJ,Bunger R,et al. Mechanisms of pyruvate inhibition of oxidant-induced apoptosis in human endothelial cells[J].Microvasc Res,2003,66 (2):91-101.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn