Fps zm1

Eight‐week‐old male C57BL/6J mice (n = 45, weight 25‐30 g) were obtained from the Animal Center of Chongqing Medical University. Mice were housed in a specific pathogen‐free mouse facility on a 12‐hour light‐dark cycle, with ad libitum access to food and water. Mice were randomly divided into three groups (n = 15 per group): Control group, DM group and DM+ FPS‐ZM1 group. Diabetic mice were induced as previously reported with some modifications,34 after a 12‐hour fast, mice received a single 150 mg/kg intraperitoneal injection of STZ (Sigma, St. Louis, MO, USA). Control mice received an equivalent volume of 0.9% saline injection. Fasting blood glucose was measured 3, 7, 10 and 20 days after STZ injection using ACCU‐CHEK Test Strips (Roche Ltd). Mice with fasting blood glucose above 300 mg/dL were considered as diabetic model. FPS‐ZM1 which can cross the blood‐brain barrier is the high‐affinity RAGE‐specific blocker. As previously described with some modifications, 3 months after diabetes induction, mice in the DM+FPS‐ZM1 group received 1 mg/kg/d intraperitoneal injection of FPS‐ZM1 (0.1 mg/mL) (Cayman Chemical, USA) and mice in other groups received an equivalent volume of 0.9% saline injection for 4 weeks.34, 35, 36, 37 Then all mice were killed.

In this study the following substances were used: Paclitaxel (PCT, Cayman Chemical Company, USA), a chemotherapeutic agent (15 (link)); FPS-ZM1 (Cayman Chemical Company, USA), a RAGE antagonist at doses of 25 μg, 50 μg, and 100 μg (16 ); LPS-RS (Invivogen, USA), a TLR4 antagonist at doses of 0.5 μg and 1 μg (14 (link)); Minocycline (Sigma-Aldrich, USA), a microglia inhibitor at doses of 5 μg and 10 μg (17 (link)); Fluorocitrate (Invivogen, USA), an astrocyte inhibitor at doses of 150 pmol and 300 pmol (14 (link)); SML0543 (Sigma-Aldrich, USA), p38 MAPK pathway inhibitor at doses of 1.5 nmol and 3 nmol (18 (link)); PDTC (Sigma-Aldrich, USA), a NF-kB inhibitor at doses of 30 μg and 60 μg and administered i.t. (19 (link)), and recombinant HMGB1 protein (Sigma-Aldrich, USA), at doses of 50 ng and 100 ng (20 (link)). PCT, FPS-ZM1 and SML0543 were diluted in sterile saline and DMSO (2%), and the other drugs were diluted in saline.