Objective To analyze the protective effect of picroside Ⅱ (Pic-Ⅱ) on myocardial injury in septic shock rats by regulating the cyclic guanylate adenylate synthetase (cGAS)-stimulator of interferon genes (STING) signaling pathway.
Methods Rats were randomly separated into six groups: Sham group, model group, low, medium, and high Pic-Ⅱ treatment groups, and activator group, with 10 rats in each group. Except the Sham group, the other groups received cecal ligation and perforation surgery to construct a rat model of septic shock. Ultrasound echocardiography was applied to detect the cardiac function of rats in each group. HE staining was applied to observe pathological changes in myocardial tissue, and TUNEL staining was applied to observe myocardial cell apoptosis. The kit method was applied to detect myocardial injury markers, including cardiac troponin Ⅰ (cTnⅠ), brain natriuretic peptide (BNP), and creatine kinase-MB (CK-MB). Enzyme-linked immunosorbent assay (ELISA) was applied to measure interleukin (IL)-1β, IL-8, and tumor necrosis factor-α (TNF-α) in myocardial tissue, and Western blot was applied to measure cGAS-STING pathway proteins in myocardial tissue.
Results Compared with Sham group, the model group showed myocardial fiber disorder, myocardial cell degeneration and necrosis, decreased the left ventricular fraction shorting (LVFS) and left ventricular ejection fraction (LVEF), increased left ventricular end diastolic diameter (LVEDD) and myocardial cell apoptosis rate, and increased level of cTnⅠ, BNP, CK-MB, IL-1β, IL-8, TNF-α, cGAS, STING, p-TANK-binding kinase 1(TBK1)/TBK1, and phosphorylated-interferon regulatory factor 3 (p-IRF3)/interferon regulatory factor 3 (IRF3) (P＜0.05). Compared with the model group, the degree of myocardial injury in low, medium, and high Pic-Ⅱ treatment groups was reduced, and the arrangement of myocardial cells was restored to a regular pattern; the LVFS and LVEF were increased, the LVEDD and myocardial cell apoptosis rate were reduced, and the cTnⅠ, BNP, CK-MB, IL-1β, IL-8, TNF-α, cGAS, STING, p-TBK1/TBK1, and p-IRF3/IRF3 were reduced (P＜0.05). Compared with the high Pic-Ⅱ treatment group, the activator group had further aggravated myocardial injury, reduced LVFS and LVEF, increased LVEDD and myocardial cell apoptosis rate, and increased expression of cTnⅠ, BNP, CK-MB, IL-1β, IL-8, TNF-α, cGAS, STING, p-TBK1/TBK1, and p-IRF3/IRF3 (P＜0.05).
Conclusion Pic-Ⅱ can protect against myocardial injury in septic shock rats, reduce cardiac dysfunction, and myocardial cell apoptosis and inflammation. The mechanism of action may be related to the inhibition of cGAS-STING signaling pathway.
