Vitamin C Protects Against Myocardial Damage Induced by Sepsis by Regulating the JAK2/STAT3 and NF-κB Signaling Pathways

Previous studies have shown that vitamin C (VC) has a protective effect on sepsis-induced myocardial injury (SIMI); however, the mechanism of this effect remains unclear. This study aimed to evaluate the effects of VC on SIMI in rats. Sprague-Dawley rats were randomly divided into three groups: sham operation, cecum ligation and perforation (CLP), and VC groups. Cardiac function was assessed using the echocardiography and hematoxylin and eosin staining. Levels of serum inflammatory cytokines, superoxide dismutase, and malondialdehyde were measured via enzyme-linked immunosorbent assay. AutoDock Vina was utilized for molecular docking to analyze the binding mechanism of VC with Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) protein. Protein expression of JAK2/STAT3 and NF-κB was assessed via Western blot, immunohistochemistry, or immunofluorescence staining. First, echocardiography and hematoxylin and eosin staining showed that VC alleviated SIMI in rats. Second, VC decreased interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and malondialdehyde levels but increased superoxide dismutase and IL-10 levels in CLP-induced SIMI as measured via enzyme-linked immunosorbent assay. Third, VC reduced cardiomyocyte apoptosis in SIMI rats as shown by Western blot and immunohistochemistry staining, and decreased the expression of cleaved caspase-3 and Bax while increasing the expression of Bcl-2 in CLP-induced SIMI. Finally, molecular docking analysis indicated a strong and stable affinity of VC for JAK2/STAT3 and NF-κB signaling pathways. Western blot and immunofluorescence results showed that VC decreased the phosphorylation levels of JAK2, STAT3, NF-κB, and IκB kinaseα/β in SIMI rats. These results suggest that VC attenuates CLP-induced SIMI through its anti-inflammatory and antiapoptotic effects, mediated by regulation of the JAK2/STAT3 and NF-κB pathways.