Department of Hepatobiliopancreatic Surgery, Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center and Department of Emergency, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Wuhou District, Chengdu, Sichuan Province 610041, People's Republic of China.
J Endocrinol. 2013 Jun 1;218(1):75-84. doi: 10.1530/JOE-12-0568. Print 2013 Jul.
Islets are exceptionally susceptible to ischemia-reperfusion injury, an increased incidence of primary graft nonfunctionality, and β-cell death during a transplant procedure. Therefore, islets require protection during the early stages of the transplant procedure. Based on the beneficial vascular and anti-inflammatory activity of adiponectin, we hypothesize that adiponectin protects islet cells against ischemia-reperfusion injury and graft dysfunction after transplantation. To examine the effects of adiponectin on the resistance of islet ischemia-reperfusion injury, we used the islet hypoxia-reoxygenation injury model and performed kidney subcapsular syngeneic islet transplants to assess the islets' vitality and function. Furthermore, we utilized lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced damage to islet cells to model the inflammation of post-transplant ischemia-reperfusion injury and transplanted islets in adiponectin knockout mice to explore whether the protective action of adiponectin is involved in TNFα production and nuclear transcription factor-κB (NF-κB) activation. Adiponectin suppressed TNFα production and IκB-α phosphorylation; decreased hypoxia-reoxygenation and LPS-induced and TNFα-induced islet apoptosis; and improved islet function in vivo and in vitro. Our results demonstrate that adiponectin protects the islet from injury. We show that islet protection occurs in response to ischemia-reperfusion and is dependent on the suppression of islet production by TNFα through cyclooxygenase 2 and the inhibition of the TNFα-induced NF-κB activation pathways.
胰岛对缺血再灌注损伤、原发性移植物无功能增加和移植过程中β细胞死亡极为敏感。因此，胰岛在移植过程的早期需要保护。基于脂联素的有益的血管和抗炎活性，我们假设脂联素可以保护胰岛细胞免受缺血再灌注损伤和移植后的移植物功能障碍。为了研究脂联素对胰岛缺血再灌注损伤的抵抗作用，我们使用胰岛缺氧再复氧损伤模型，并进行肾被膜下同种异体胰岛移植，以评估胰岛的活力和功能。此外，我们利用脂多糖 (LPS) 诱导或肿瘤坏死因子 α (TNFα) 诱导的胰岛细胞损伤来模拟移植后缺血再灌注损伤的炎症，并在脂联素敲除小鼠中移植胰岛，以探讨脂联素的保护作用是否涉及 TNFα 产生和核转录因子-κB (NF-κB) 激活。脂联素抑制 TNFα 的产生和 IκB-α 的磷酸化；减少缺氧再复氧以及 LPS 诱导和 TNFα 诱导的胰岛细胞凋亡；并改善体内和体外的胰岛功能。我们的结果表明脂联素可以保护胰岛免受损伤。我们发现，胰岛的保护作用是对缺血再灌注的反应，并且通过环氧化酶 2 依赖于 TNFα 对胰岛产生的抑制以及抑制 TNFα 诱导的 NF-κB 激活途径而发生。
