Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect

作者：Qing Yao, Xue Jiang, Zhiwei Huang, Qing-Hua Lan, Lifen Wang, Rui Chen, Xin-Ze Li, Longfa Kou, Helin Xu, Ying‐Zheng Zhao · 发表于：Transplantation · 年份：2019 · DOI：10.1097/tp.0000000000002882 · 被引用次数：55 · 研究领域：Pancreatic function and diabetes、Diabetes and associated disorders、Heme Oxygenase-1 and Carbon Monoxide

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ...