Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, Japan.
PLoS One. 2013 Aug 9;8(8):e70259. doi: 10.1371/journal.pone.0070259. eCollection 2013.
Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.
Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.
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), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-2'-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration.
The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be 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.
最近的研究表明，降低氧化应激对于实现胰岛移植的成功至关重要。硫氧还蛋白-1（TRX）是一种多功能氧化还原活性蛋白，已被报道可抑制氧化应激。此外，它还具有抗炎和抗细胞凋亡作用。在本研究中，我们研究了 TRX 对胰岛移植后早期移植物丢失的影响。
对两组链脲佐菌素诱导的糖尿病小鼠进行门静脉内胰岛移植：对照组和 TRX 组。此外，TRX 转基因（Tg）小鼠被交替用作胰岛供体或受体。
与 TRX-Tg 供体和对照组相比，TRX 组的血糖水平变化明显更低（p<0.01）。TRX 组的葡萄糖耐量和残留移植物质量明显更好。TRX 显著抑制了血清白细胞介素-1β水平（p<0.05），尽管没有观察到抗凋亡或抗趋化作用。值得注意的是，无论是否给予 TRX，胰岛输注后 8-羟基-2'-脱氧鸟苷水平均未升高。
本研究表明，在胰岛移植物上过度表达 TRX 不足以改善移植效果。相比之下，TRX 对受体的给药通过抑制血清白细胞介素-1β水平对移植胰岛移植物发挥保护作用。然而，单独的 TRX 似乎不足以完全防止胰岛移植后早期移植物丢失。因此，我们提出将 TRX 与其他抗炎治疗相结合可能是改善胰岛移植疗效的一种有前途的方案。
