2022 Fiscal Year Final Research Report

Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats

Research Project

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Project/Area Number	18K08919
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55060:Emergency medicine-related
Research Institution	Okayama University
Principal Investigator	Shimizu Hiroko 岡山大学, 医学部, 客員研究員 (80423284)
Co-Investigator(Kenkyū-buntansha)	森松博史岡山大学, 医歯薬学域, 教授 (30379797) 井上一由岡山大学, 医学部, 客員研究員 (10624413) 高橋徹岡山県立大学, 保健福祉学部, 教授 (40252952)
Project Period (FY)	2018-04-01 – 2023-03-31
Keywords	急性腎不全 / 横紋筋融解症 / ヘムオキシゲナーゼ-1 / 塩化スズ
Outline of Final Research Achievements	We have demonstrated for the first time that SnCl2 pretreatment ameliorates RM-AKI induced upon injecting glycerol into the hind limbs of rats. This could be attributed to the early, enhanced, and persistent induction of HO-1 expression by SnCl2 in the kidney as SnCl2 is a kidney-specific inducer of HO-1. We also showed that renal expression of ALAS1 and Bach1 in SnCl2- pretreated animals was maintained almost to the same extent as that in normal animals, while this expression was significantly suppressed in saline-pretreated animals. ALAS1 is downregulated by heme, and Bach1 is exported from the nucleus in complexes that contain increased intracellular heme content. Thus, our findings suggest that overexpression of HO-1, the rate-limiting enzyme in heme catabolism, by SnCl2 pretreatment confers protection against rat RM-AKI as it degrades the excess amount of intracellular free heme, a pro-oxidant released from myoglobin.
Free Research Field	救急医学
Academic Significance and Societal Importance of the Research Achievements	横紋筋融解症に伴う急性腎傷害(RM-AKI)では、筋ミオグロビン由来の遊離ヘムがその病態形成に関わっていることが報告されている。塩化スズは腎特異的に、ヘム代謝の律速酵素であるHO-1を誘導する薬剤である。グリセロール筋肉注射による RM-AKI ラットモデルを用い、塩化スズによる腎保護作用と症機序を、その作解明することは、災害現場でも利用可能なRM-AKIに対する治療法の開発につながり、さらには早期治療開始により腎傷害の重症化予防、救命率の向上などに大いに貢献できると考える。本研究は、塩化スズによる RM-AKI の治療法の開発を進める上で重要な基礎研究と考える。