The study of n-3PUFAs protecting the intestinal barrier in rat HS/R model

Lipids in Health and Disease

Jieshou Li¹  Ning Li¹  Xinying Wang¹  Yang Li¹ 

[1] Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, 305 Zhongshan East Road, Nanjing 210002, China

关键词: n-3 PUFAs;    I-FABP;    Occludin protein;    Tight junction;    Resuscitation;    Hemorrhagic shock;   

Others  :  1152050
DOI  :  10.1186/1476-511X-13-146

 received in 2014-06-14, accepted in 2014-08-05,  发布年份 2014

【 摘 要 】

Background

N-3 PUFAs have been demonstrated in vitro it could prevent the intestinal tight junctions (TJs) from the ischemia/re-perfusion injury and the inflammatory reaction injury. The purpose of this study was to evaluate the protection of n-3 PUFAs on the intestinal TJs in the rat model of hemorrhagic shock followed by resuscitation.

Methods

Male SD rats (n = 72; 250 ~ 300 g) were randomly divided into 6 groups: SHAM, hemorrhagic shock (HS), hemorrhagic shock/resuscitation (HS/R), ω-6 group, ω-3 group and ω-3 treatment group. Shock was induced, and a mean arterial pressure was maintained at 35 to 40 mmHg for 60 minutes. Resuscitation was carried out by returning half of the shed blood and Ringer’s lactate solution. In ω-6 and ω-3 group, Intralipid or fish oil (0.2 g/Kg), respectively, was infused 30 minutes after shock. And fish oil was infused with resuscitation in ω-3 treatment group. Half of each group was killed at 30 minutes and 4 hours after resuscitation, respectively. The serum samples and the intestinal sample was collected for further examination.

Result

There is no difference between ω-3, ω-3 treatment and sham group in Chiu’s score, but the other three groups have higher scores than they did. Compared with HS, HSR and ω-6 group, ω-3 and ω-3 treatment group showed most intact in intestinal mucoscal villi and TJs through HE, SEM and LSCM. The levels of IL-6 and TNF-α of bowel tissue in ω-3 and ω-3 treatment group were significantly lower than HS and HSR groups’. At the time point of 30 min, the levels of serum endotoxin were dramatically higher in HS、HSR and ω-6 groups when compared with ω-3, ω-3 treatment and sham group. However, it in ω-3 group was greater than sham and HS group until 4 hours.

Conclusion

Fish oil pretreatment before resuscitation showed a beneficial effect to the intestinal TJs and atteunated inflammation after H/R in HS/R rat model and is better than ω-6 PUFAs did.

【 授权许可】

   
2014 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Henao FJ, Daes JE, Dennis RJ: Risk factors for multiorgan failure: a case–control study. J Trauma 1991, 31:74-80.
• [2]Deitch EA: Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery 2002, 131:241-244.
• [3]Baker JW, Deitch EA, Li M, Berg RD, Specian RD: Hemorrhagic shock induces bacterial translocation from the gut. J Trauma 1988, 28:896-906.
• [4]Fink MP, Delude RL: Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level. Crit Care Clin 2005, 21:177-196.
• [5]Han X, Fink MP, Yang R, Delude RL: Increased iNOS activity is essential for intestinal epithelial tight junction dysfunction in endotoxemic mice. Shock 2004, 21:261-270.
• [6]Xu DZ, Lu Q, Deitch EA: Nitric oxide directly impairs intestinal barrier function. Shock 2002, 17:139-145.
• [7]Heller A, Koch T, Schmeck J, van Ackern K: Lipid mediators in inflammatory disorders. Drugs 1998, 55:487-496.
• [8]Gadek JE, DeMichele SJ, Karlstad MD, Pacht ER, Donahoe M, Albertson TE, Van Hoozen C, Wennberg AK, Nelson JL, Noursalehi M: Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome: enteral nutrition in ARDS study group. Crit Care Med 1999, 27:1409-1420.
• [9]Grimm H, Schott J, Schwemmle K: [Development of an immuno-neutral lipid emulsion for optimal postoperative management of intensive care patients]. Langenbecks Archiv fur Chirurgie Supplement Kongressband Deutsche Gesellschaft fur Chirurgie Kongress 1998, 115:599-604.
• [10]Lee S, Gura KM, Kim S, Arsenault DA, Bistrian BR, Puder M: Current clinical applications of omega-6 and omega-3 fatty acids. Nutr Clin Pract 2006, 21:323-341.
• [11]Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U: Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001, 286:944-953.
• [12]Pontes-Arruda A, Demichele S, Seth A, Singer P: The use of an inflammation-modulating diet in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of outcome data. JPEN J Parenter Enteral Nutr 2008, 32:596-605.
• [13]Calder PC: n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006, 83:1505S-1519S.
• [14]Marik PE: Total splanchnic resuscitation, SIRS, and MODS. Crit Care Med 1999, 27:257-258.
• [15]Chiara O, Pelosi P, Segala M, Turconi MG, Brazzi L, Bottino N, Taccone P, Zambelli M, Tiberio G, Boswell S, Scalea TM: Mesenteric and renal oxygen transport during hemorrhage and reperfusion: evaluation of optimal goals for resuscitation. J Trauma 2001, 51:356-362.
• [16]el Zakaria R, Hurt RT, Matheson PJ, Garrison RN: A novel method of peritoneal resuscitation improves organ perfusion after hemorrhagic shock. Am J Surg 2003, 186:443-448.
• [17]Porter JM, Ivatury RR: In search of the optimal end points of resuscitation in trauma patients: a review. J Trauma 1998, 44:908-914.
• [18]Wang X, Pan L, Lu J, Li N, Li J: N-3 PUFAs attenuate ischemia/reperfusion induced intestinal barrier injury by activating I-FABP-PPARgamma pathway. Clin Nutr 2012, 31:951-957.
• [19]Simopoulos AP: Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002, 21:495-505.
• [20]Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chiolero RL: Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med 2007, 33:789-797.
• [21]Michaeli B, Berger MM, Revelly JP, Tappy L, Chiolero R: Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. Clin Nutr 2007, 26:70-77.
• [22]Yang R, Tan X, Thomas AM, Steppacher R, Qureshi N, Morrison DC, Van Way CW III: Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related genes in hemorrhagic shock. JPEN J Parenter Enteral Nutr 2007, 31:32-36.
• [23]Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959, 37:911-917.
• [24]Morrison WR, Smith LM: Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol. J Lipid Res 1964, 5:600-608.
• [25]Pace-Asciak CR: One-step rapid extrachive methylation of plasma nonesterified fatty acids for gas chromatographic analysis. J Lipid Res 1989, 30:451-454.
• [26]Grimminger F, Führer D, Papavassilis C, Schlotzer E, Mayer K, Heuer K, Kiss L, Walmrath D, Piberhofer D, Lübbecke F, Krämer HJ, Stevens J, Schütterle GWS: Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis. Clin Invest 1993, 23:706-715.
• [27]Mayser P, Mayer K, Mahloudjian M, Benzing S, Krämer H-J, Schill W-B, Seeger WFG: A double-blind, randomized, placebocontrolled trial of n-3 vs. n-6 fatty acid based lipid infusion in atopic dermatitis. JPEN J Parenter Enteral Nutr 2002, 26:151-158.
• [28]Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN: Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970, 101:478-483.
• [29]Guttman JA, Li Y, Wickham ME, Deng W, Vogl AW, Finlay BB: Attaching and effacing pathogen-induced tight junction disruption in vivo. Cell Microbiol 2006, 8:634-645.