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研究発表を行った学会；
　　　米国腎臓学会 Kidney week 2016
　　　2016年11月17日〜20日（Chicago, USA）
タイトル；Long-acting albumin-thioredoxin fusion protein suppresses AKI-associated acute lung injury.
発表者；西田　健人　氏
　　　（熊本大学　薬学教育部　薬剤学分野）
要旨；
Background
Respiratory complications are common after acute kidney injury (AKI) and are associated with increased mortality. Therefore, an effective strategy for preventing AKI-induced acute lung injury (ALI) due to increasing oxidative stress and inflammatory response is highly desirable. Thioredoxin-1 (Trx) is a redox-active protein that has anti-oxidative and anti-inflammatory properties. Although, Trx has great potential for use as a therapeutic agent against several types of oxidative stress-related diseases, its short half-life (1 h in the mouse) limits its clinical application. To overcome this problem, we produced a recombinant fusion protein that is comprised of human serum albumin (HSA) and Trx (HSA-Trx), and examined its protective effects.
Methods
HSA-Trx was expressed in Pichia expression system. Renal ischemia/reperfusion (I/R) induced ALI mice were used to observe lung injury.
Results
A pharmacokinetic study of HSA-Trx or Trx in mice showed that the plasma retention and lung distribution of Trx was markedly improved by fusion with HSA. The renal I/R group showed not only a remarkable increase in blood urea nitrogen and serum creatinine levels, but also demonstrated neutrophil infiltration in the lung and increased protein concentration in bronchoalveolar lavage fluid (BALF) compared to the sham group. In contrast, the HSA-Trx administration clearly resulted in a decrease in the number of neutrophils in the lung and BALF protein concentration compared with the PBS treatment group. HSA-Trx also suppressed the elevation of interleukin-6 in plasma and the neutrophil chemokines CXCL1/CXCL2 and oxidative stress in lung.
Conclusion
HSA-Trx has potential for use in the treatment of AKI-induced ALI via its extended effects of modulating oxidative stress and inflammation.