Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats
Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats
复制标题
DOI：
10.1016/j.surg.2022.07.021
复制
发表时间：
2022-10-05
期刊：
影响因子：
3.8
通讯作者：
Naito, Hiromichi
中科院分区：
文献类型：
--
作者：
Nojima, Tsuyoshi;Obara, Takafumi;Naito, Hiromichi
背景：肠移植物易发生缺血再灌注损伤，导致黏膜屏障功能丧失和移植物衰竭。胆绿素具有多种抗氧化组织损伤的细胞保护功能。由于粘膜层是缺血再灌注损伤的主要部位，因此通过腔内递送试剂的粘膜靶向策略可能是有益的。我们测试了胆绿素作为标准保存溶液的辅助剂是否可以防止缺血再灌注损伤。方法：Lewis大鼠冷冻保存6小时后进行原位同基因肠移植。在冷冻保存前立即将含胆绿素的生理盐水（10 mM）或不含胆绿素的生理盐水注入移植物的管腔。结果：缺血-再灌注损伤引起的肠黏膜损伤导致肠绒毛变钝、糜烂等严重形态学改变，再灌注后3小时肠屏障功能明显丧失。胆绿素可显著改善这些粘膜变化。胆绿素还能有效抑制白细胞介素-6、诱导型一氧化氮合酶和C-C基序趋化因子2的信使rna上调。此外，胆绿素处理阻止了claudin-1的表达丧失，claudin-1是一种跨膜紧密连接屏障蛋白。胆绿素处理的移植物14天存活率明显高于盐水处理的对照组（83.3% vs 38.9%, P 1/4 .030）。结论：本研究表明，光传递胆绿素在大鼠小肠移植过程中具有有益的作用，可能是一种有吸引力的器官移植治疗选择。(c) 2022作者。Elsevier Inc.出版。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
Background: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemiareperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury. Methods: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 mM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. Results: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P 1/4 .030). Conclusion: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).