2022 Fiscal Year Final Research Report
Luminal Administration of a Water-soluble Carbon Monoxide–releasing Molecule (CORM-3) Mitigates Ischemia/Reperfusion Injury in Rats Following Intestinal Transplantation
| Project/Area Number |
20K22953
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-09-11 – 2023-03-31
|
| Keywords | 小腸移植 / 虚血再灌流障害 / 一酸化炭素 / CO-releasing molecules / soluble guanylyl cyclase / carbon monoxide |
|---|
| Outline of Final Research Achievements |
Orthotopic syngeneic intestinal transplantation was performed in Lewis rats following 6h of cold preservation in Ringer solution or UW solution. Saline containing CORM-3 (100μM) or its inactive counterpart (iCORM-3) was intraluminally introduced in the intestinal graft before cold preservation. Histopathological analysis of CORM-3 treated grafts attenuated an erosion and blunting of the intestinal villi. CORM-3 significantly inhibited upregulation of proinflammatory mRNA levels, ameliorated intestinal morphological changes, and improved mucosal barrier function. Additionally, CORM-3 grafts increased recipient survival rates. Pharmacological blockade of soluble guanylyl cyclase activity significantly reversed the protective effects conferred by CORM-3, indicating that CO partially mediates its therapeutic actions via soluble guanylyl cyclase activation. Our study demonstrates that luminally delivered CORM-3 provides beneficial effects in cold-stored rat small intestinal grafts.
|
| Free Research Field |
救急医学
|
| Academic Significance and Societal Importance of the Research Achievements |
小腸は他の臓器よりも虚血再灌流障害に弱く、移植後も急性・慢性拒絶反応が高い傾向にあることから、移植後虚血再灌流障害の抑制は小腸移植の発展に必要不可欠と考えられてきた。一酸化炭素(CO)は抗炎症作用を持つシグナルガスとして臨床応用が期待されているが、気体では細胞内窒息に中毒性が懸念される。一方、CO供与体であるCORMsはCO-Hb濃度を上げることなく、標的組織内にCOを取り込ませることが可能となる。また、本方法はCORM含有保存的をグラフト腸管内に充填するだけであり、簡便で臨床的に汎用性の高い方法となり得る可能性がある。本方法の有用性が実証されれば、医療経済的観点からも意義が大きいと思われる。
|
