Dehydrocorydaline Protects Against Sepsis-Induced Myocardial Injury Through Modulating the TRAF6/NF-κB Pathway
We try to investigate effect and mechanism of dehydrocorydaline (Deh), an alkaloidal component isolated from Rhizoma corydalis, in treating sepsis-mediated myocardial injuries. Lipopolysaccharide (LPS) was come to construct an in-vitro sepsis-myocardial injuries models H9C2 cardiomyocytes. The in-vivo type of sepsis in C57BL/6 rodents was caused by intraperitoneal injection of Escherichia coli (E. coli). The in-vitro as well as in-vivo models were given Deh in various concentrations, correspondingly. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemistry (IHC) staining were come to assess the histopathological changes from the heart. ELISA was put on assess the amounts of inflammatory factors, including IL-6, IL-1ß, TNFa, IFN?, and oxidized factors SOD, GSH-PX within the plasma or culture medium. Western blot was utilized to determine the expressions of Bax, Bcl2, Caspase3, iNOS, Nrf2, HO-1, TRAF6, NF-?B in heart tissues and cells. The viability of H9C2 cardiomyocytes was detected through the CCK8 method and BrdU assay. The ROS level within the H9C2 cardiomyocytes were determined using immunofluorescence. Consequently, Deh treatment improved the survival of sepsis rodents, reduced TUNEL-labeled apoptosis of cardiomyocytes. In vitro, Deh enhanced the viability of LPS-caused H9C2 cardiomyocytes and inhibited cell apoptosis. Furthermore, Deh demonstrated significant anti-inflammatory and anti-oxidative stress functions via decreasing IL-1ß, IL-6, TNFa, and IFN? levels, mitigating ROS level, up-controlling Nrf2/HO-1, SOD, and GSH-PX expressions dose-dependently. Mechanistically, Deh inhibited TRAF6 expression and also the phosphorylation of NF-?B p65. The intervention having a specific inhibitor of TRAF6 (C25-140) or NF-?B inhibitor (BAY 11-7082) markedly repressed the protective effects mediated by Deh. To conclude, Deh restrains sepsis-caused cardiomyocyte injuries by inhibiting the TRAF6/NF-?B path.