Fig. 5

The combination of RORα/CMBs and melatonin treatment optimized the benefits to improve cardiac injury beyond melatonin alone in rats with fatal sepsis. (A) Experimental scheme and timeline for sepsis model construction and interventions. UTMD-mediated RORα delivery (40 µg/kg) was repeated at one-day intervals 1 day, 3 days, and 5 days before CLP surgery. Intravenous melatonin 2.5 mg/kg was given 30 min before surgery and 12 h after the surgery. Heart tissue and blood were taken 20 h after CLP surgery. (B) Representative images of echocardiography at 16 h after CLP surgery. The left ventricle ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated (n = 7–10). (C) Melatonin levels in serum (n = 7–8) and cardiac tissues (n = 4) at 20 h after CLP surgery. (D) Serum LDH and CK-MB levels, markers of cellular injury, were evaluated using ELISA kits 20 h after CLP surgery (n = 7–8). (E) Serum levels of TNF-α and IL-1β were elevated to reflect systemic inflammation (n = 5). (F) Representative hematoxylin and eosin (H&E, scale bar of 100 μm) and TUNEL staining images of heart sections (n = 3, ~ 12 views per group, scale bar of 50 μm). (G) Rats with sepsis were observed for 3.5 days after CLP surgery. The survival rates were analyzed using the Kaplan-Meier curve and log-rank test (n = 11–16 per group)