Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita, 879-5593, Japan.
Inflammation. 2012 Feb;35(1):249-58. doi: 10.1007/s10753-011-9311-y.
Autophagy is a natural process by which a cell maintains homeostasis, usually taking place unnoticed by adjacent cells. Glucose is involved in a negative feedback loop in autophagy. Autophagy is characterized by the induction and secretion of HMGB1, yet the nature of the inflammatory response during and the effect of glucose administration on autophagy are not well understood. Systemic inflammation was induced in experimental animals by LPS injection (7.5 mg/kg) followed by a continuous infusion of either 1%, 5%, or 25% glucose. Autophagy was visualized by immunohistochemistry 12 h after LPS injection. Likewise, protein levels of microtubule-associated protein light chain 3 (LC3)-II, autophagy-related protein 7 (Atg7), and high-mobility group box 1 (HMGB1) were assayed by western blot analysis. We found that autophagy increased in liver tissue in response to LPS-induced systemic inflammation. However, protein levels decreased in rats receiving LPS and a 5% glucose solution. Our results suggest that LPS-induced systemic inflammation increases autophagy in liver cells, potentially involving the upregulation of LC3-II, Atg7, and HMGB1. We also show that a 5% glucose infusion reduces autophagy. We propose that maintaining serum glucose levels with an adequate glucose dose improves systemic inflammation by reducing autophagy.
自噬是一种细胞维持体内平衡的自然过程，通常在相邻细胞察觉不到的情况下发生。葡萄糖参与自噬的负反馈回路。自噬的特征是诱导和分泌 HMGB1，但自噬过程中的炎症反应的性质以及葡萄糖给药对自噬的影响尚不清楚。通过 LPS 注射（7.5mg/kg）诱导实验动物的全身炎症，然后连续输注 1%、5%或 25%葡萄糖。LPS 注射后 12 小时通过免疫组织化学观察自噬。同样，通过 Western blot 分析测定微管相关蛋白轻链 3（LC3）-II、自噬相关蛋白 7（Atg7）和高迁移率族蛋白 B1（HMGB1）的蛋白水平。我们发现，LPS 诱导的全身炎症反应导致肝组织中的自噬增加。然而，在接受 LPS 和 5%葡萄糖溶液的大鼠中，蛋白水平下降。我们的结果表明，LPS 诱导的全身炎症增加了肝细胞中的自噬，可能涉及 LC3-II、Atg7 和 HMGB1 的上调。我们还表明，5%葡萄糖输注会减少自噬。我们提出，通过用适当剂量的葡萄糖维持血清葡萄糖水平，可以通过减少自噬来改善全身炎症。
