Abstract：Objective: Validation of dibutyryl cyclic adenosine (Bucladesine)-mediated changes in vasodilator-stimulated phosphoprotein (VASP) in relation to cardiomyocyte action in septic mice. Methods: A mouse model of sepsis was constructed by cecum ligation perforation, and the experiment was divided into: control (Con), sham-operated (Sham), model (Mod) and Bucladesine (Buc) groups. Biochemical assays were performed to detect tissue malondialdehyde (MDA) and superoxide dismutase (SOD) levels in serum and myocardium. Flow cytometry was performed to detect reactive oxygen species (ROS) levels in myocardial tissue and mitochondrial membrane potential in cells. TUNEL staining was performed to detect myocardial tissue apoptosis. Hematoxylin-eosin (HE) staining was performed to observe myocardial lesions. p-VASP expression levels in myocardial tissues were measured by Western blot. Results: Compared with the control and sham groups, the model group showed significantly higher MDA levels (P<0.05), lower SOD levels (P<0.05), higher ROS levels (P<0.05), higher p-VASP and VASP protein expression levels (P<0.05) in serum and myocardial tissue, myocardial fiber breakage, laxity, increased gap, and increased TUNEL brown area coloring. Compared with the model group, the serum and myocardial tissue in the Buc group showed significantly lower MDA content (P<0.05), higher SOD content (P<0.05), lower ROS content (P<0.05), lower p-VASP and VASP protein expression levels (P<0.05), tighter myocardial fibers, and reduced TUNEL brown area coloration. Conclusion: Inhibition of p-VASP by Bucladesine can alleviate the myocardial dysfunction caused by sepsis, which mechanism of action is associated with modulation of cardiomyocyte mitochondrial activity and enhancement of cellular antioxidant capacity.
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2023, Vol. 29 
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