ABSTRACT
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.
ABSTRACT
Objective@#To investigate the clinical value of transvaginal three-dimensional ultrasonography in the differential diagnosis of benign and malignant endometrial diseases after menopause.@*Methods@#From April 2015 to April 2017, the imaging data of transvaginal three-dimensional ultrasonography of 184 patients with benign and malignant breast tumors in the Second People's Hospital of Yuhang District were retrospectively analyzed.The peak systolic flow velocity, resistance index, peak systolic velocity, intimal arterial resistance index and blood flow display rate of uterine artery of benign and malignant endometrial diseases were compared.@*Results@#The accuracy, sensitivity and specificity of transvaginal three-dimensional ultrasonography in the diagnosis of endometrial diseases were 91.30%(168/184), 92.00%(46/50), 91.04%(122/134), respectively.There were no statistically significant differences in the peak systolic flow velocity, resistance index, peak systolic velocity of patients with benign and malignant endometrial diseases by transvaginal three-dimensional ultrasonography(t=1.17, 0.88, 0.51, all P>0.05). The intimal arterial resistance index of patients with malignant endometrial diseases by transvaginal three-dimensional ultrasonography was significantly lower than patients with benign endometrial diseases(t=2.59, P<0.05). The blood flow display rates of uterine artery of patients with malignant endometrial diseases by transvaginal three-dimensional ultrasonography were 19.40%(26/134), 92.00%(46/50). The blood flow display rate of uterine artery of patients with malignant endometrial diseases by transvaginal three-dimensional ultrasonography was significantly higher than patients with benign endometrial diseases(χ2=7.26, P<0.05).@*Conclusion@#Transvaginal three-dimensional ultrasonography in the differential diagnosis of benign and malignant endometrial diseases after menopause has higher accuracy, sensitivity and specificity.