Hagiwara Satoshi, Iwasaka Hideo, Koga Hironori, Hasegawa Akira, Kudo Kyousuke, Kusaka Jyunya, Oyama Yoshimasa, Noguchi Takayuki
Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
Biomed Res. 2010 Oct;31(5):263-71. doi: 10.2220/biomedres.31.263.
The dysregulated metabolism associated with diabetes mellitus (DM) impairs membrane trafficking events in the liver, including the process of autophagy, which is an essential ongoing cellular process that is highly regulated by nutrients, endocrine factors, and signaling pathways. High-mobility group box 1 (HMGB1) is a nuclear protein with a known role in systemic inflammation and the related various organ injuries. However, its relationship to autophagy is not well understood. The aim of this study was to investigate the effects of inflammation injury on autophagy in the liver in a rat model of DM. DM was induced in animals with streptozotocin, followed four weeks later by induction of inflammation by LPS injection. At 12 h after LPS administration, autophagy was assessed by immunohistochemistry and Western blot analysis of microtubule-associated protein light chain 3 (LC3)-II, as well as transmission electron microscopy. Expression of HMGB1 was also examined by immunohistochemistry and Western blot analysis. Western blot analysis of liver tissue revealed that levels of LC3-II and HMGB1 protein increased in DM rats subjected to LPS-induced inflammation compared with non-DM rats. Autophagy was particularly enhanced in DM rats. Thus, autophagy might be related to progression to organ injury in patients with DM, and inflammation in these patients might be associated with over-induction of autophagy and increased HMGB1 expression.
与糖尿病（DM）相关的代谢失调会损害肝脏中的膜转运过程，包括自噬过程，自噬是一个持续进行的重要细胞过程，受营养物质、内分泌因子和信号通路的高度调控。高迁移率族蛋白B1（HMGB1）是一种核蛋白，在全身炎症及相关的各种器官损伤中发挥作用。然而，其与自噬的关系尚不清楚。本研究的目的是在糖尿病大鼠模型中研究炎症损伤对肝脏自噬的影响。用链脲佐菌素诱导动物患糖尿病，四周后通过注射脂多糖诱导炎症。在给予脂多糖后12小时，通过免疫组织化学和微管相关蛋白轻链3（LC3）-II的蛋白质印迹分析以及透射电子显微镜评估自噬。还通过免疫组织化学和蛋白质印迹分析检测HMGB1的表达。肝脏组织的蛋白质印迹分析显示，与非糖尿病大鼠相比，脂多糖诱导炎症的糖尿病大鼠中LC3-II和HMGB1蛋白水平升高。糖尿病大鼠的自噬尤其增强。因此，自噬可能与糖尿病患者器官损伤的进展有关，并且这些患者的炎症可能与自噬过度诱导和HMGB1表达增加有关。
