Abstract: Objective: To study the effects of salvianolic acid on the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in myocardium tissue of atrial fibrillation rats and extracellular signal-regulating enzymes 1/2-nuclear transcription factor-κB (ERK1/2-NF-κB) signaling pathway, and to explore the possible mechanism of salvianolic acid in the preventing and treating atrial fibrillation. Methods: Forty-eight SD rats were randomly divided into control group, atrial fibrillation group and salvianolic acid group, with 16 rats in each group.The rat models of atrial fibrillation were established by intravenous injection of calcium chloride-acetylcholine mixture in the sublingual vein. The rats in salvianolic acid group were administrated with Salvianolic acid (4 mg·kg^-1·d^-1) by gavage and the rats in control group and atrial fibrillation group were intragastrically administered with an equal amount of normal saline, once a day, for 4 weeks. Hematoxylin-Eosin(HE) staining was used to observe the histopathological changes of myocardium tissue of the rats. Masson staining was used to observe the myocardial fibrosis. The expression levels of matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) proteins in myocardium tissue of the rats in various groups were measured by immunohistochemical staining. Western bloting method was used to determine the expression levels of VCAM-1, ICAM-1, ERK1/2, phosphorylated ERK1/2(p-ERK1/2), NF-κB and phosphorylated NF-κB (p-NF-κB) in myocardium tissue of the rats in various groups. Results: The HE staining results showed that there was no obvious abnormality in the myocardial cells of the rats in control group. In atrial fibrillation group, myocardial interstitial tissue was increased, and inflammatory cell infiltration was found. Compared with atrial fibrillation group,the myocardial interstitial tissue in salvianolic acid group was slightly more, and inflammatory cell infiltration was not obvious. The Masson staining results showed that the myocardial interstitial collagen fibers of the rats in control group were normal, and the myocardial interstitial collagen fibers of the rats in atrial fibrillation group were increased significantly; compared with atrial fibrillation group, the myocardial interstitial collagen fibers of the rats in salvianolic acid group were significantly reduced. Compared with control group, the expression levels of MMP-2, MMP-9,VCAM-1, ICAM-1, p-ERK1/2 and p-NF-κB proteins in myocardium tissue of the rats in atrial fibrillation group and salvianolic acid group were increased (P<0.05). Compared with atrial fibrillation group, the expression levels of MMP-2, MMP-9, VCAM-1, ICAM-1, p-ERK1/2 and p-NF-κB proteins in myocardium tissue of the rats in salvianolic acid group were reduced (P<0.05). The expression levels of MMP-2 and MMP-9 proteins in myocardium tissue of the rats in atrial fibrillation group were positively correlated with the expression levels of VCAM-1(r=0.435, P<0.01;r=0.512, P<0.05) and ICAM-1(r=0.486,P<0.01;r=0.579, P<0.01) proteins. Conclusion: Salvianolic acid can reduce the levels of VCAM-1 and ICAM-1, inhibit myocardial fibrosis, and exert the protective effect on atrial fibrillation by inhibiting the activation of ERK1/2-NF-κB signaling pathway in myocardium tissue of the atrial fibrillation rats.

Key words: salvianolic acid, atrial fibrillation, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, extracellular signal-regulating enzymes1/2-nuclear transcription factor-κB signaling pathway, matrix metalloproteinase