Influence of CXCL12/CXCR4 biological axis on myocardial fibrosis in mice with chronic viral myocarditis

GUO Chunyan; HAN Bo; LIANG Hao; ZHANG Xiaojing; WANG Yi

doi:10.3969/j.issn.1002-266X.2017.17.007

Abstract：Objective To study the relationship between the CXCL12/CXCR4 biological axis and myocardial fibrosis in chronic viral myocarditis(CVMC).Methods Thirty 4-week-old Balb/c mice were randomly divided into the control group(n=10)and CVMC group(n=20).The mice in the CVMC group were infected with Coxsachie virus B3(CVB3,1×10.9/mL)to establish CVMC models on day 0,14 and 28 with the volume of 0.20,0.25 and 0.30 mL,respectively.The mice in the control group received the equal volume normal of saline.After anesthesia,the heart rate(HR),left ventricular end-diastolic internal diameter(LVDD),left ventricular end-systolic internal diameter(LVSD),and peak velocity of aorta(Vp)at least 3 consecutive cardiac cycles were measured by echocardiography on day 42.Meanwhile,the ejection fraction(EF)and fractional shortening(FS)were calculated.Mice were killed after echocardiographic analysis.Then we counted the ratio of heart weight to body weight(HW/BW).Heart slides were stained with collagen specific picrosirius red staining or HE staining.The collagen volume fraction(CVF)was calculated.The protein expression of CXCL12 and CXCR4 was determined by Western blotting.The mRNA expression of type I collagen and type Ⅲ collagen was determined by RT-PCR.Results Compared with the control group,the CVF,the mRNA expression of type I collagen and type Ⅲ collagen and the protein expression of CXCL12 and CXCR4 significantly increased in the CVMC group(all P<0.05).The CVF was positively correlated with CXCL12 and CXCR4 protein expression in the CVMC group(r=0.79,0.60,all P<0.05).Conclusion CXCL12/CXCR4 biological axis is closely related to CVMC myocardial fibrosis.