School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.
Transplantation. 2019 Dec;103(12):2486-2496. doi: 10.1097/TP.0000000000002882.
Islet transplantation is a promising option for the treatment of type 1 diabetes. However, the current lack of practical techniques for the isolated islets preservation still hampers the advancement of life-saving islet transplantation. Islet suffers from internal or external stimuli-induced oxidative stress and subsequent inflammation during preservation, which leads to disappointing outcomes regarding islet yield, survival, and function. Reactive oxygen species (ROS) overproduction is the primary cause of oxidative stress that induces islet loss and dysfunction. Thus, in this article, we hypothesized that an endogenous antioxidant, bilirubin, that could efficiently scavenge ROS and inhibit inflammatory reactions could be beneficial for islet preservation.
Herein, we studied the effect of bilirubin on the hypothermic preserved (4°C) islets and evaluate the islets viability, insulin secretory function, oxidative stress levels, and in vivo transplantation performance.
Bilirubin could prevent cellular damages during short-term preservation and maintain the cocultured islets viability and function. The protective role of bilirubin is associated with its antioxidative ability, which dramatically increased the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreased the levels of ROS and malondialdehyde. Diabetic mice transplanted with bilirubin preserved islets were normoglycemic for 28 days, even overmatched the diabetic mouse transplanted with fresh islets. Mice receiving bilirubin cocultured islets required the least time to achieve normoglycemia among all groups and exhibited minimum inflammatory responses during the early transplantation stage.
By utilizing bilirubin, we achieved highly viable and functional islets after hypothermic preservation to reverse diabetes in mice.
胰岛移植是治疗 1 型糖尿病的一种很有前途的选择。然而，目前缺乏实用的胰岛分离保存技术，仍然阻碍了挽救生命的胰岛移植的进展。胰岛在保存过程中会受到内部或外部刺激引起的氧化应激和随后的炎症反应，导致胰岛产量、存活率和功能令人失望。活性氧（ROS）的过度产生是引起氧化应激导致胰岛丧失和功能障碍的主要原因。因此，在本文中，我们假设一种内源性抗氧化剂胆红素可以有效地清除 ROS 并抑制炎症反应，这可能对胰岛保存有益。
本文研究了胆红素对低温保存（4°C）胰岛的影响，并评估了胰岛的活力、胰岛素分泌功能、氧化应激水平和体内移植性能。
胆红素可以防止短期保存过程中的细胞损伤，并维持共培养胰岛的活力和功能。胆红素的保护作用与其抗氧化能力有关，它显著增加了抗氧化酶（超氧化物歧化酶和谷胱甘肽过氧化物酶）的活性，降低了 ROS 和丙二醛的水平。接受胆红素保存胰岛移植的糖尿病小鼠在 28 天内血糖正常，甚至超过了接受新鲜胰岛移植的糖尿病小鼠。接受胆红素共培养胰岛的小鼠在所有组中达到血糖正常所需的时间最短，并且在早期移植阶段表现出最小的炎症反应。
通过使用胆红素，我们实现了低温保存后高活力和功能正常的胰岛，从而逆转了小鼠的糖尿病。
