深低温停循环(deep hypothermic circulatory arrest,DHCA)是外科复杂心脏手术的一种重要辅助技术,是术中脑保护的措施之一,并为外科手术提供便利的操作条件。然而这项技术所导致的并发症也不容忽视,其中肠损伤的发生虽较为隐匿,但是给患者带来巨大的痛苦并明显降低术后生活质量。研究表明,DHCA 导致肠道发生缺血再灌注损伤,引起肥大细胞活化释放炎性介质,破坏肠黏膜上皮屏障,最终导致肠损伤。

Deep hypothermic circulatory arrest is an important asistant technique for complex cardiac surgery, which creates convenient operating conditions for surgery, it is also one of the measures to protect 1the brain during operation. However, the complications caused by this technique cannot be ignored, it should be noticed that the occurrence of intestinal injury is relatively insidious, but it brings great pain to patients and significantly reduces the quality of life after operation. Studies have shown that intestinal ischemia reperfusion injury was induced by DHCA, It causes mast cells to activate and release many inflammatory mediators that destroy the intestinal mucosal epithelium barrier, and eventually lead to intestinal injury.

关键词: 深低温停循环; 肠损伤; 肥大细胞

Key words: Deep hypothermic circulatory arrest; intestinal injury; mast cell

登录后 ,请手动点击刷新查看全文内容。 没有账号,
登录后 ,请手动点击刷新查看图表内容。 没有账号,
1. Gutsche JT, Ghadimi K, Patel PA, et al. New frontiers in aortic therapy: focus on deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth, 2014, 28(4): 1159-1163.
2. Grenz A, Eltzschig HK. Mast cells and intestinal injury: a novel link between hypoxia and inflammation. Crit Care Med, 2013, 41(9): 2246-2248.
3. Cooper WA, Duarte IG, Thourani VH, et al. Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis. Ann Thorac Surg, 2000, 69(3): 696-702.
4. Yang MQ, Ma YY, Ding J, et al. The role of mast cells in ischemia and reperfusion injury. Inflamm Res, 2014, 63(11): 899-905.
5. . Di Marco L, Murana G, Leone A, et al. Con-debate: short circulatory arrest times in arch reconstructive surgery: is simple retrograde cerebral perfusion or hypothermic circulatory arrest as good or better than complex antegrade cerebral perfusion for open distal involvement or hemi-arch. J Vis Surg, 2018. 4: 46.
6. Etz CD, Luehr M, Kari FA, et al. Selective cerebral perfusion at 28 degrees C--is the spinal cord safe? Eur J Cardiothorac Surg, 2009, 36(6): 946-955.
7. Juremalm M, Olsson N, Nilsson G. Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors CCR1 and CCR4. Biochem Biophys Res Commun, 2002, 297(3): 480-485.
8. Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol, 2011, 12(11): 1035-1044.
9. 刘东方, 张春光, 吴健民. 肥大细胞脱颗粒机制研究进展. 国外医学(临床生物化学与检验学分册), 2004, 25(2): 137-139.
10. Amin K. The role of mast cells in allergic inflammation. Respir Med, 2012, 106(1): 9-14.
11. Yu Y, Blokhuis BR, Garssen J, et al. Non-IgE mediated mast cell activation. Eur J Pharmacol, 2016, 778: 33-43.
12. Bischoff SC. Physiological and pathophysiological functions of intestinal mast cells. Semin Immunopathol, 2009, 31(2): 185-205.
13. Anand P, Singh B, Jaggi AS, et al. Mast cells: an expanding pathophysiological role from allergy to other disorders. Naunyn Schmiedebergs Arch Pharmacol, 2012, 385(7): 657-670.
14. Karhausen J, Qing M, Gibson A, et al. Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest. Crit Care Med, 2013, 41(9): e200-e210.
15. Tsunooka N, Maeyama K, Hamada Y, et al. Bacterial translocation secondary to small intestinal mucosal ischemia during cardiopulmonary bypass. Measurement by diamine oxidase and peptidoglycan. Eur J Cardiothorac Surg, 2004, 25(2): 275-280.
16. Solligård E, Wahba A, Skogvoll E, et al. Rectal lactate levels in endoluminal microdialysate during routine coronary surgery. Anaesthesia, 2007, 62(3): 250-258.
17. Zarins CK, Skinner DB. Circulation in profound hypothermia. J Surg Res, 1973, 14(2): 97-104.
18. Jakob SM. Splanchnic blood flow in low-flow states. Anesth Analg, 2003, 96(4): 1129-1138.
19. Eltzschig HK, Sitkovsky MV, Robson SC. Purinergic signaling during inflammation. N Engl J Med, 2012, 367(24): 2322-2333.
20. Kats S, Schönberger JP, Brands R, et al. Endotoxin release in cardiac surgery with cardiopulmonary bypass: pathophysiology and possible therapeutic strategies. An update. Eur J Cardiothorac Surg, 2011, 39(4): 451-458.
21. Efthymiou CA, Weir WI. Salmonella sepsis simulating gastrointestinal ischaemia following cardiopulmonary bypass. Interact Cardiovasc Thorac Surg, 2011, 12(2): 334-336.
22. Deitch EA. Gut lymph and lymphatics: a source of factors leading to organ injury and dysfunction. Ann N Y Acad Sci, 2010, 1207 Suppl 1: E103-E111.
23. Boros M. Microcirculatory dysfunction during intestinal ischemia-reperfusion. Acta Physiol Hung, 2003, 90(4): 263-279.
24. Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon, 2012, 10(6): 350-356.
25. Kuehn HS, Gilfillan AM. G protein-coupled receptors and the modification of FcepsilonRI-mediated mast cell activation. Immunol Lett, 2007, 113(2): 59-69.
26. Suzuki Y, Yoshimaru T, Inoue T, et al. Role of oxidants in mast cell activation. Chem Immunol Allergy, 2005, 87: 32-42.
27. Murray DB, Gardner JD, Brower GL, et al. Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation, and myocardial remodeling in rats. Am J Physiol Heart Circ Physiol, 2004, 287(5): H2295-H2299.
28. Rork TH, Wallace KL, Kennedy DP, et al. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol, 2008, 295(5): H1825-H1833.
29. Zimmermann H. Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol, 2000, 362(4-5): 299-309.
30. Venkatesha RT, Berla Thangam E, Zaidi AK, et al. Distinct regulation of C3a-induced MCP-1/CCL2 and RANTES/CCL5 production in human mast cells by extracellular signal regulated kinase and PI3 kinase. Mol Immunol, 2005, 42(5): 581-587.
31. Lin L, Bankaitis E, Heimbach L, et al. Dual targets for mouse mast cell protease-4 in mediating tissue damage in experimental bullous pemphigoid. J Biol Chem, 2011, 286(43): 37358-37367.
32. Overman EL, Rivier JE, Moeser AJ. CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PLoS One, 2012, 7(6): e39935.
33. Anderson JM, Van Itallie CM. Physiology and function of the tight junction. Cold Spring Harb Perspect Biol, 2009, 1(2): a002584.
34. Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol, 2017, 14(1): 9-21.
35. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa. Physiol Rev, 2007, 87(2): 545-564.
36. Shen L, Weber CR, Raleigh DR, et al. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol, 2011, 73: 283-309.
37. Marchiando AM, Shen L, Graham WV, et al. Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J Cell Biol, 2010, 189(1): 111-126.
38. Li S, Guan J, Ge M, et al. Intestinal mucosal injury induced by tryptase-activated protease-activated receptor 2 requires β-arrestin-2 in vitro. Mol Med Rep, 2015, 12(5): 7181-7187.
39. Liu D, Gan X, Huang P, et al. Inhibiting tryptase after ischemia limits small intestinal ischemia-reperfusion injury through protease-activated receptor 2 in rats. J Trauma Acute Care Surg, 2012, 73(5): 1138-1144.
40. Gan X, Xing D, Su G, et al. Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation. Oxid Med Cell Longev, 2015, 2015: 167014.