Thioredoxin-1による移植後早期膵島障害の抑制に関する研究

抄録

【Objective】Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and antiapoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.
【Methods】Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control group and a TRX group. Moreover, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.
【Results】The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups （p<0.01）. Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1β （p<0.05）, though neither antiapoptotic nor antichemotactic effects were observed. Notably, no increase in the 8-hydroxy-2'‐deoxyguanosine level was observed after islet infusion, regardless of TRX administration.
【Conclusions】The present study demonstrates that an overexpression of TRX on the islet grafts is in sufficient to improve engraftment. In contrast, TRX administration to recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be also insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.