Exploration of the Mechanism of Anshen Dingxin Granule in Intervening Ventricular Premature Beats Based on the PI3K/AKT Pathway

YUE Chaochong; LI Xiaohui; LI Xingyuan; LIU Gang; LI Yizhuo; JIANG Lei; SONG Miaoyu; ZHU Cuiling; SUN Yanqin

Abstract：Objective To investigate the effects of An Shen Ding Xin granules on ventricular premature beats(VPB)induced by isoproterenol(ISO)and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway in rats.Methods Rats were randomly divided into six groups(n=10 per group):control group,model group,propranolol group,and low-,medium-,and high-dose Anshen Dingxin granule groups.Two hours after gavage,all groups except the control group were injected with ISO to induce VPB for 7 consecutive days.The control and model groups received 0.9％sodium chloride solution.The following parameters were analyzed:Time and frequency of VPB occurrence recorded by electrocardiogram(ECG);Pathological changes in myocardial tissues observed by hematoxylin-eosin(HE)and masson staining;Ultrastructure of myocardial tissues examined by transmission electron microscopy;Serum levels of TNF-α,IL-6,and IL-1β measured by enzyme-linked immunosorbent assay(ELISA);Expression of connexin 43(Cx43)in myocardial tissues detected by immunohistochemistry;Expression levels of PI3K,AKT,and Cx43 mRNA and protein determined by Western blot and RT-qPCR.Results Compared with the control group,the model group showed:Increased frequency of VPB and higher arrhythmia scores(P<0.01);Significant pathological damage and fibrosis in myocardial tissues;Elevated serum levels of TNF-α,IL-6,and IL-1β(P<0.01);Reduced expression of Cx43 protein(P<0.01);Decreased expression levels of PI3K,AKT,and Cx43 mRNA and protein(P<0.01).Compared with the model group,the propranolol group and Anshen Dingxin granule groups exhibited:Delayed onset of VPB,reduced frequency,and lower arrhythmia scores(P<0.05);Ameliorated myocardial pathological damage and fibrosis;Decreased serum levels of TNF-α,IL-6,and IL-1β(P<0.05);Increased expression of Cx43 protein(P<0.05);Elevated expression levels of PI3K,AKT,and Cx43 mRNA and protein(P<0.05).Conclusion Anshen Dingxin granule can effectively alleviate ISO-induced VPB in rats,potentially through regulating the PI3K/AKT signaling pathway,suppressing inflammatory responses,reducing myocardial injury,and enhancing Cx43 protein expression to maintain normal cardiac electrophysiological activity.