Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Curr Opin Organ Transplant. 2013 Jun;18(3):298-303. doi: 10.1097/MOT.0b013e32835ef1eb.
Ischemia-reperfusion injury is inevitable during intestinal transplantation and can negatively affect the transplant outcome. Here, an overview is provided of the recent advances in the pathophysiological mechanisms of intestinal ischemia-reperfusion injury and how this may impact graft survival.
The intestine hosts a wide range of microorganisms and its mucosa is heavily populated by immune cells. Intestinal ischemia-reperfusion results in the disruption of the epithelial lining, affecting also protective Paneth cells (antimicrobials) and goblet cells (mucus), and creates a more hostile intraluminal microenvironment. Consequently, both damage-associated molecular patterns as well as pathogen-associated molecular patterns are released from injured tissue and exogenous microorganisms, respectively. These 'danger' signals may synergistically activate the innate immune system. Exaggerated innate immune responses, involving neutrophils, mast cells, platelets, dendritic cells, as well as Toll-like receptors and complement proteins, may shape the adaptive T-cell response, thereby triggering the destructive alloimmune response toward the graft and resulting in transplant rejection.
Innate immune activation as a consequence of ischemia-reperfusion injury may compromise engraftment of the intestine. More dedicated research is required to further establish this concept in man and to design more effective therapeutic strategies to better tolerize intestinal grafts.
肠移植过程中不可避免会发生缺血再灌注损伤，这会对移植物的存活产生负面影响。本文就肠缺血再灌注损伤的病理生理机制的最新进展及其对移植物存活的影响进行概述。
肠道内栖息着各种各样的微生物，其黏膜中也有大量的免疫细胞。肠缺血再灌注会导致上皮细胞层破裂，同时也会影响保护性的潘氏细胞（抗菌肽）和杯状细胞（黏液），并使腔内微环境更加恶劣。因此，损伤相关分子模式和病原体相关分子模式分别从受损组织和外源性微生物中释放出来。这些“危险”信号可能协同激活固有免疫系统。固有免疫反应的过度激活，涉及中性粒细胞、肥大细胞、血小板、树突状细胞以及 Toll 样受体和补体蛋白，可能会影响适应性 T 细胞反应，从而引发针对移植物的破坏性同种免疫反应，导致移植排斥。
缺血再灌注损伤引起的固有免疫激活可能会损害肠的移植。需要进行更多的专门研究，以进一步在人体中证实这一概念，并设计更有效的治疗策略，以更好地耐受肠移植物。
