FIGURE 7.
DXZ treatment ameliorated the Deterioration of DIC caused by the overexpression of Alox5 via inhibiting ferroptosis. (A) Schematic diagram of the acute mice modelling process of DIC. (B) Representative western blots of Alox5 expression in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 6 per group). (C) Survival analysis DOX 8 day in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 10 per group). Comparison of survival curves between DOX + rAAV9‐Alox5 and rAAV9‐Alox5 + DOX + DXZ mice group using the log‐rank (Mantel–Cox) test. (D) Body weight alterations in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 10 per group). (E) Statistical results of the heart weight/tibia length (HW/TL) in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 10 per group), analysed by one‐way ANOVA with the Bonferroni post hoc test. (F,G) Representative HE staining images and the quantitative results in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 10 per group), analysed by one‐way ANOVA with the Bonferroni post hoc test. (H) Representative B‐ and M‐mode echocardiographic imaging of the heart in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 8 per group). (I–L) Analysis of LVEF, LVFS, LVEDd and LVEDs in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 8 per group), analysed by one‐way ANOVA with the Bonferroni post hoc test. (M) Representative PV loops of rAAV9‐Alox5 + DOX + DXZ, rAAV9‐Alox5 + DOX or rAAV9‐GFP + DOX mice group (n = 8 per group), analysed by one‐way ANOVA with the Bonferroni post hoc test. (N–P) Analysis of cardiac output, +dp/dt and ‐dp/dt in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 8 per group), analysed by one‐way ANOVA with the Bonferroni post hoc test. (Q–S) Serum cTnT, CK‐MB and LDH levels in rAAV9‐GFP mice group, rAAV9‐Alox5 mice group, rAAV9‐GFP + DOX mice group, rAAV9‐Alox5 + DOX mice group, or rAAV9‐Alox5 + DOX + DXZ mice group (n = 6 per group) were analysed by one‐way ANOVA with the Bonferroni post hoc test. Values represent mean ± SEM. $p < 0.05: p‐value compared between rAAV9‐GFP group and rAAV9‐GFP + DOX group, *p < 0.05: p‐value compared between rAAV9‐Alox5 + DOX group and rAAV9‐GFP + DOX group, #p < 0.05: p‐value compared between rAAV9‐Alox5 + DOX group and rAAV9‐Alox5 + DOX + DXZ group.