Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.

AIM: To explore the effect of ethanol extract of costusroot (EEC) on gastric mucosa in gastric ulcer rats and related mechanism. METHODS: The rats were randomly divided into 5 groups: normal group, model group, sucralfate group, low-EEC group and high-EEC group, and anhydrous alcohol was administrated intragastrically to replicate gastric ulcer model in groups other than the normal. Changes in the area of gastric ulcer were observed and the inhibition rate of ulcer was calculated. The pathological changes of gastric tissue were measured by HE staining, and the protein expression levels of Bax and Bcl-2 were tested by immunohistochemistry and Western blot. RESULTS: EEC inhibited the formation of ulcer area in model rats and alleviated the histopathological damage to the stomach caused by ethanol. While enhancing the expression of Bcl-2 protein (P<0.01), it effectively inhibited the overexpression of Bax (P<0.01). CONCLUSION: EEC has a strong function of anti-gastric ulcers, and its mechanism of action might be related to the regulation of the protein expression level of Bax and Bcl-2 to inhibit the apoptosis of gastri mucosal cells.