| Objective: To observe the effect of ErbB4 receptor agonist neuregulin-1βon cardiac function and cardiomyocyte apoptosis in rats with adriamycin-inducing dilated cardiomyopathy(DCM) and discuss its mechanism.Method: (1)To establish adriamycin-induced cardiomyopathy ratmodels by injected via a tail vein of adriamycin (2mg/kg .week) for 8weeks. The model rats were divided randomly into 2 groups: neuregulin-1βgroup(NRG, n=10) and model control group(DCM, n=10), nomal rats group(CON,n=10) served as control. (2)The left ventricular dimension at end-diastole(LVEDD) and left ventricular ejection fraction (LVEF) were measuredwith echocardiography at baseline and 8th weeks after intervention.Hemodynamic indexes including left end-ventricular diastolic pressure(LVEDP), maximum left ventricular developed pressure increase rate anddecrease rate were measured at the 12th week. Histopathological characteristics were observed in HE, Masson then left ventricular cardiomyocyte and collagen volume fractions(CVF) were calculated and the expression and distribution of loca ErbB4 positive cells, and the infiltration of macrophages by immunohistochemical method.(3)Contents of tumor necrosis factor-α(TNF-α), endothelin-1(ET-1) were determined by radioimmunoassay fromvenous serum and brain natriuretic peptide (BNP) by ELISA.(4)using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method and protein expression of bax and bcl-2 protein was determined by Western blot.Result: (1)Compared with the normal rats, LVEDD of the DCM rats was significantly increased [(5.50.±0.10)mm vs (7.0±0.20)mm, P<0.05] and LVEF[(85.0±1.8)% vs (66.5±2.5)%, P<0.05] was reduced inadriamycin-induced cardiomyopathy rat models. During the course of treatment at the 12th week, LVEDD in the NRG group was lower than DCM group[(6.0±0.40)mm vs (7.0±0.20)mm, P<0.05], while LVEF in the NRG groups was higher than DCM group [(80.1±1.4)% vs (66.5±2.5)%, P<0.05].(3)Compared with the DCM group, +dp/dtmax of the NRG group was increased [(4506.5±243.3)mmHg/s vs (3545.5±187.4)mmHg/s, P<0.05],and -dp/dtmax of the NRG group was also significantly increased[(-3605±189.9)mmHg/s vs (-2705.6±230.8), P<0.05]. In comparisonwith the normal group, left ventricular CVF of the DCM rats was significantly increased. Compared with the control group, the pathological scores of pancreatic edema, inflammation, hemorrhage and necrosis of DCM rats significantly increased, and compared with DCM group, these four indexes discreased significantly in NRG rats. In comparison with the normal group, the expression of ErbB4 significantly discreased and its distribution was irregulate. and compared with NRG group, the expression of ErbB4 significantly increased and its distribution was improved.(2) Compared with control group, concentration of TNF-a,ET-1 , BNP in serum were higher in DCM group.[(20.58±2.55)fmol/mlvs0, p<0.05,(88.33±2.25)pg/mlvs(43.51±3.20), p< 0.05 ,(45.41±2.38)pg/mlvs(15.32±1.48), p<0.05]; Compared with DCM group, concentration of TNF-a,ET-1,BNP in serum were lower in NRG group. [20.58±2.55)fmol/mlvs(12.70±1.15), p<0.05, (88.33±2.25) pg/mlvs (59.20±2.12), p< 0.05,(45.41±2.38) pg/mlvs(30.87±1.81), p<0.05].The index of apoptotic cardiomyocytes increased significantly in DCM group and NRG group compared with control group(p<0.05),and compared with DCM group, the index of apoptotic cardiomyocytes induced significantly in NRG group (p<0.05) ; compared with DCM group, the expressions of bcl-2 protein increased significantly(p<0.05),and the expression of bax protein induced significantly (p<0.05)in NRG group.Conclusion: ErbB4 receptor agonist neuregulin-1βcan improve cardiac function in SD rats which reduced by DCM. To inhibit some failure cytokines in serum and enhance the expression of ErbB4 in myocardium and regulation some protein of apoptosis may be its mechanism.
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