Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury.
Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury.
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DOI：
10.1038/srep14471
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发表时间：
2015-09-28
影响因子：
4.6
通讯作者：
Maruyama T
中科院分区：
文献类型：
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作者：
Nishida K;Watanabe H;Ogaki S;Kodama A;Tanaka R;Imafuku T;Ishima Y;Chuang VT;Toyoda M;Kondoh M;Wu Q;Fukagawa M;Otagiri M;Maruyama T
横纹肌溶解相关急性肾损伤（阿基）是一种严重危及生命的疾病。因此，需要采取更有效的战略来预防这一现象。硫氧还蛋白-1（Trx）是一种氧化还原活性和巨噬细胞移动抑制因子（MIF）调节蛋白，在血液中的保留时间短。我们研究了与人血清白蛋白（HSA-Trx）基因融合的长效Trx对甘油诱导的阿基的肾保护作用。与单独的PBS、HSA或Trx相比，静脉内HSA-Trx预处理减弱了甘油诱导的肾功能下降。HSA-Trx引起肾小管损伤和肾小管上皮细胞凋亡阳性细胞数量减少。肾超氧化物，8-羟基脱氧鸟苷，硝基酪氨酸和血浆Cys 34-半胱氨酸化白蛋白明显抑制HSA-Trx治疗。HSA-Trx在降低TNF-α和IL-6水平之前抑制血浆MIF水平的升高。在LLC-PK 1细胞中，HSA-Trx降低肌红蛋白诱导的活性氧和乳酸脱氢酶释放水平。HSA-Trx处理导致致死甘油处理小鼠的存活率增加三倍。在甘油注射后1和3小时给药后HSA-Trx产生了显着的肾脏保护作用。这些结果表明，HSA-Trx通过其调节氧化应激和MIF的延长作用，具有用于治疗横纹肌溶解相关阿基的潜力。
Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-α and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-treated mice. The post-administration of HSA-Trx at 1 and 3 hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-associated AKI via its extended effects of modulating oxidative stress and MIF.