Fig. 6. Resolvin-D2 improves muscle force and function to a higher level than glucocorticoids in the mdx mouse model.
a Timeline of daily intraperitoneal (ip) injection of either Resolvin-D2 (RvD2, 5 μg/kg/day), prednisone (pred, 2 mg/kg/day) or vehicle (ctrl) into mdx mice. b, e Hang test performance (time mice can hold on an inverted grid) of mdx mice following daily ip treatment for 7 days (b) (Ctrl vs. Pred, p = 0.7962; Ctrl vs. RvD2, p < 0.0001; Pred vs. RvD2, p < 0.0001), and 21 days (e) (Ctrl vs. Pred, p = 0.9931; Ctrl vs. RvD2, p = 0.0058; Pred vs. RvD2, p = 0.0059). c, f Isometric contractile properties of EDL muscles showing the peak tetanic force following 7 days (c) (150 Hz: Ctrl vs. Pred, p = 0.3439; Ctrl vs. RvD2, p < 0.0001; Pred vs. RvD2, p < 0.0001) or 21 days (f) of treatment (150 Hz: Ctrl vs. Pred, p = 0.5265; Ctrl vs. RvD2, p = 0.0004; Pred vs. RvD2, p = 0.0027) and d, g specific muscle force of EDL muscle of mdx mice treated for 7 days (d) (150 Hz: Ctrl vs. Pred, p = 0.0634; Ctrl vs. RvD2, p < 0.0001; Pred vs. RvD2, p = 0.0027), or 21 days (g) (150 Hz: Ctrl vs. Pred, p = 0.8125; Ctrl vs. RvD2, p = 0.0003; Pred vs. RvD2, p = 0.0007). h Timeline of weekly ip injection of either RvD2 (5 μg/kg), prednisone (2 mg/kg) or vehicle into mdx mice. i, j Isometric contractile properties of EDL muscles showing the peak tetanic force (i) (150 Hz: Ctrl vs. Pred, p = 0.1908; Ctrl vs. RvD2, p = 0.0028; Pred vs. RvD2, p = 0.0697), and specific force (j) (150 Hz: Ctrl vs. Pred, p = 0.1537; Ctrl vs. RvD2, p = 0.0007; Pred vs. RvD2, p = 0.0318) of mdx mice treated weekly for 21 days. k Timeline of weekly ip injection of O-1918 (Gpr18 antagonist; 2 mg/kg) alone or prior to the injection of RvD2 (5 μg/kg) or vehicle. l, m Isometric contractile properties of EDL muscles showing the peak tetanic force (l) (150 Hz: Ctrl vs. O-1918, p = 0.2004; Ctrl vs. RvD2 + O-1918, p = 0.7759; Ctrl vs. RvD2, p < 0.0001; RvD2 + O-1918 vs. RvD2, p < 0.0001), and specific force (m) (150 Hz: Ctrl vs. O-1918, p = 0.7553; Ctrl vs. RvD2 + O-1918, p = 0.3862; Ctrl vs. RvD2, p < 0.0001; RvD2 + O-1918 vs. RvD2, p < 0.0001) of mdx mice treated weekly for 21 days. b–j RvD2 = blue triangles, pred = red squares, and Ctrl = black circles. Data are presented as mean ± SEM, n = 4 (except n = 3 for i, j, l, and m) mice per group/time-point. Experiments were performed in technical duplicates using one-way (b, e) or two-way (c, d, f, g, i, j, l, and m) ANOVA uncorrected Fisher’s LSD test. All data were analyzed with a 95% confidence interval. **p < 0.01; ****p < 0.0001 for b and e. *p < 0.05 compared with the vehicle, and †p < 0.05 compared with prednisone for c, d, f, g, i, and j. *p < 0.05 for RvD2 compared with either Ctrl or O-1918 or RvD2 + O-1918 (l, m).