ABSTRACT
Objective To study the role of transforming growth factor-β1 (TGF-β1),connective tissue growth factor (CTGF)and endothelin-1 (ET-1) in myocardial tissues of the mice with myocardial fibrosis induced by coxsachievirus B3 (CVB3) and the effect of Carvedilol intervention for it in acute stage and chronic phase of viral myocarditis.Methods Forty male BALB/c mice were randomly divided into 4 groups (10 cases in each group):control group,model group,Carvedilol acute phase intervention group,the chronic phase intervention group.Mice in model group and Carvedilol intervention groups were inoculated with CVB3 (100TCID50/0.1 mL) by peritoneal injection fortnightly.Mice in control group were given normal saline(NS) instead equivalently.Mice were poured Carvedilol (10 mg/kg per day for 2 weeks) from the second day in acute phase intervention group and from the fourth week in the chronic phase intervention group,while mice of control group and model group were poured with equivalent NS instead.At the end of 6 weeks,mice were sacrificed.Heart weight index (HWI) was determined.The collagen volume fraction (CVF) of left ventricular myocardial tissue were examined after Masson staining.Expressions of ET-1,TGF-β1 and CTGF were detected by enzyme linked immunosorbent assay and immunohistochemistry staining respectively; the mRNA expression was tested by reverse transcription-polymerase chain reaction.Results Compared with the control group,HWI and CVF of model group increased significantly(all P ＜ 0.01),those of the intervention groups decreased than those of the model group(all P ＜ 0.01),and in the acute phase those of the intervention group were significantly lower than those in chronic phase intervention group(all P ＜ 0.05).The expressions of TGF-β1,CTGF,ET-1 and their mRNA in model group were increased significantly than those in the control group(all P ＜0.01),and were decreased in acute and the chronic phase intervention group than those in model group(all P ＜0.01),while those were significantly lower in acute phase intervention group than those in chronic phase intervention group (all P ＜ 0.01).Conclusions TGF-β1,CTGF and ET-1 may be involved in myocardial fibrosis induced by CVB3.Compared with the chronic phase intervention,the acute phase intervention of Carvedilol can reduce myocardial fibrosis more efficiently by down-regulating the excessive expression of inflammatory factors.
ABSTRACT
s:Objective To investigate the possible role of basic ifbroblast growth factor (bFGF) and transforming growth factorβ1 (TGF-β1) in mice with Coxsackie viral myocarditis and their relationship. Methods Eighty male BALB/c mice, 4 weeks old, were divided randomly into study group (n=40) and control group (n=40). The study group was repeated intraperitoneally injected with Coxasckie viral B3 to establish the model of viral myocarditis, while the control group was injected with virus-free Eagle’s medium in the same period. On the 7th, 14th, 28th and 42th day after the ifrst injection, 8 alive mice selected randomly from each group were sacriifced to examine the myocardial collagen volume fraction (CVF) by Masson dyeing, and to detect the protein and mRNA expression of bFGF and TGF-β1 by RT-PCR and immunohistochemistry. The correlations were analyzed. Results At each time point, the expressions of protein and mRNA of bFGF and TGF-β1 both in study group were signiifcantly higher than those in control group (P<0.01), and gradually increased over time. The expressions of protein and mRNA of bFGF and TGF-β1 were positively correlated with CVF (r=0.86~0.95, all P<0.01). In addition, the expressions of protein and mRNA of bFGF also had positive correlation with the expression of protein and mRNA of TGF-β1 (r=0.94, 0.92, P<0.01). Conclusion bFGF and TGF-β1 may promote the occurrence and development of myocardial ifbrosis in viral myocarditis, which may provide a new target for future treatment of myocardial ifbrosis.