Luminal preloading with hydrogen‐rich saline ameliorates ischemia‐reperfusion injury following intestinal transplantation in rats
Luminal preloading with hydrogen‐rich saline ameliorates ischemia‐reperfusion injury following intestinal transplantation in rats
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富氢盐水腔内预载可改善大鼠肠移植后的缺血再灌注损伤
DOI：
10.1111/petr.13848
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发表时间：
2020
影响因子：
1.3
通讯作者：
Naito Hiromichi
中科院分区：
文献类型：
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作者：
Yamamoto Hirotsugu;Aokage Toshiyuki;Igawa Takuro;Hirayama Takahiro;Seya Mizuki;Ishikawa‐Aoyama Michiko;Nojima Tsuyoshi;Nakao Atsunori;Naito Hiromichi
长时间的肠道冷藏会导致相当大的粘膜破坏，这可能会促进细菌的易位，并对移植受体造成危及生命的感染。肠道有一个腔内腔室，这可能是干预的目标，但尚未得到充分的研究。氢气具有器官保护作用，近年来已被用于肠移植等多项临床和基础研究。在这项研究中，我们旨在研究腔内给予富氢盐水对肠移植冷IR损伤的细胞保护作用。对Lewis大鼠进行冷缺血6小时的等基因肠移植。保存前立即在腔内引入富氢盐水（h2浓度为5ppm）或生理盐水。再灌注后3小时切除移植物肠进行分析。对照移植物的组织病理学分析显示绒毛变钝和糜烂。腔内氢明显减弱了这些粘膜变化。IR损伤引起的肠黏膜损伤导致肠屏障功能在再灌注后3小时明显恶化。然而，氢处理可以有效地防止渗透率的下降。氢处理可减轻IR诱导的促炎细胞因子mrna（如IL - 6）的上调。Western blot结果显示，氢处理可调节跨膜蛋白ZO‐1的丢失。移植肠腔内给予富氢盐水可调节大鼠移植肠的IR损伤。利用腔内氢的新策略成功消除肠道IR损伤可能易于临床应用，并将显著改善移植后患者的护理。
Prolonged intestinal cold storage causes considerable mucosal breakdown, which could bolster bacterial translocation and cause life‐threatening infection for the transplant recipient. The intestine has an intraluminal compartment, which could be a target for intervention, but has not yet been fully investigated. Hydrogen gas exerts organ protection and has used been recently in several clinical and basic research studies on topics including intestinal transplantation. In this study, we aimed to investigate the cytoprotective efficacy of intraluminally administered hydrogen‐rich saline on cold IR injury in intestinal transplantation. Isogeneic intestinal transplantation with 6 hours of cold ischemia was performed on Lewis rats. Hydrogen‐rich saline (H2concentration at 5 ppm) or normal saline was intraluminally introduced immediately before preservation. Graft intestine was excised 3 hours after reperfusion and analyzed. Histopathological analysis of control grafts revealed blunting of the villi and erosion. These mucosal changes were notably attenuated by intraluminal hydrogen. Intestinal mucosa damage caused by IR injury led to considerable deterioration of gut barrier function 3 h post‐reperfusion. However, this decline in permeability was critically prevented by hydrogen treatment. IR‐induced upregulation of proinflammatory cytokine mRNAs such as IL‐6 was mitigated by hydrogen treatment. Western blot revealed that hydrogen treatment regulated loss of the transmembrane protein ZO‐1. Hydrogen‐rich saline intraluminally administered in the graft intestine modulated IR injury to transplanted intestine in rats. Successful abrogation of intestinal IR injury with a novel strategy using intraluminal hydrogen may be easily clinically applicable and will compellingly improve patient care after transplantation.