Figure 1: Development of diabetes in C57BL/6 mice treated with streptozotocin (STZ) and hypoxia.

(A) Chemical structure of shikonin. (B) A schematic of STZ-induced diabetes combined with hypoxia is shown. Intraperitoneal (IP) injections of STZ (55 mg⁄kg) were given daily to C57BL/6 mice for five days. A control group was injected with an equivalent volume of citrate buffer only. After induction of diabetes, mice were randomly separated into five groups; a control group was placed under normoxic condition, whereas the other four groups were placed in a sealed hypoxia chamber and supplied with 10% oxygen. Three of the four hypoxia groups received 0.5 mg/kg, 5 mg/kg, or 50 mg/kg of shikonin daily per os. The final hypoxia group was given 1% DMSO only. Electroretinograms (ERG) were taken on days 3, 12, and 25, while fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT) were performed weekly until day 28. Successful development of experimental diabetes in the STZ-treated mice was confirmed by blood glucose measurement at days 0 and 28. (C) General features of blood glucose and HbA1c levels in DM/hypoxic C57BL/6 mice treated with/without 0.5 mg/kg, 5 mg/kg, or 50 mg/kg of shikonin are presented. Data are expressed as mean ± SD of five animals per group. ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 vs normal control by ANOVA.