Project/Area Number |
18K16021
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Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53050:Dermatology-related
|
Research Institution | Kanazawa University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | 虚血再灌流障害 / NO / iNOS / 創傷治癒 / 褥瘡 |
Outline of Final Research Achievements |
Ischemia-reperfusion (IR) is considered a key mechanism of pressure ulcer. The purpose of this study is to assess a role of cytokines and in the ulcer formation process using a cutaneous IR mouse model. Both IFN- gamma-deficient and IL-6-deficient mice that received IR cycles showed improvement of tissue damage. In these mutant mice, reduced macrophage infiltration and increased expression of iNOS, TNF-alfa and MCP-1 were observed. Wild type mice injected anti- IFN-gamma mAb or anti-IL-6 mAb intravenously showed improvement ulcer size. In vitro culture of macrophages from wild type mice stimulated with IFN- gamma resulted in increased production of NO. The ratio of M1 macrophages were more dominant in early phase of IR cycles at the wound site, whereas M2 macrophages ratio was gradually increased as time passes. This study indicates that IR injury is mediated by M1 and M2 macrophage infiltration that is induced by inflammatory cytokines including IFN-gamma and IL-6.
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Academic Significance and Societal Importance of the Research Achievements |
褥瘡の発生には単に局所の虚血だけでなく,再灌流時の組織障害も重要であり、そのメカニズムを検証することは褥瘡の予防や治療において重要である。褥瘡の誘引として、血流障害、ずれなどの刺激が従来考えられているが、本研究では、サイトカインにより誘導されるM1およびM2マクロファージの浸潤と,引き続いて起こるiNOSの発現とNOの産生も,褥瘡の誘引の一つとして考えられた。サイトカインとそれによる炎症を抑制することが虚血再灌流により引き起こされる皮膚障害を軽減する治療ターゲットとなりうる。
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