| Objective: Coxsackie-adenovirus receptor (CAR), a kind of 365-amino acid transmembrane protein, is the common receptor for coxsackievirus B group (CVB) and adenovirus (ADV). It plays an important mediated role in cardiac myocytes with CVB or ADV infection. The purpose of this study was to investigate the kinetic features of CAR expression in mice with viral myocarditis (VMC), its significance in the pathogenesis of viral myocarditis, and the influence of astragaloside intervention on CAR expression.Methods: (1) Eighty BALB/C mice were divided into two groups: the infected group and a control group. Mice in the infected group (n=70) were inoculated intraperitoneally with o.1 mLof 1× 10~2TCID50 CVB3 diluted in Eagle's minimal essential medium (EMEM) solution. Control mice were treated with 0.1 mL of EMEM. Ten infected mice were sacrificed on days 3,7,15 and 30 after inoculation, and the control mice were killed on day 30 postinoculation. The expression levels of CAR mRNA and protein in VMC mice were examined by RT-PCR and immunohistochemistry, respectively. At the same time, the concentration of serum IL-1β was detected by ELISA. (2) Twenty mice were equally divided into a rIL-1β group that rIL-1β (1μg/0.1mL), administered hypodermic on day 0 to 4, and a control group with PBS .All mice were killed on day 10 and hearts were removed. The expression levels of CAR mRNA and protein in the myocardium were detected by RT-PCR and immunohistochemistry, respectively. (3) 100 BALB/C mice were randomly divided into 6 groups: normal control group (group A,n=10), high-dose control group (group B,n=10), myocarditic control group (group C,n=20), low-dose intervention group (groupD,n=20), middle-dose intervention group (group E,n=20) and high-dose intervention group (group D,n=20). Mice in group A and group B were inoculated intraperitoneally with 0.1 mL of 1×10~2 TCID50 CVB3 diluted in EMEM solution, and mice in group C, D, E and F were treated with 0.1 mL of EMEM. Then, mice in group A and group B were treated with carboxymethycellulose solution and 9% astragaloside in carboxymethycellulose solution 0.1 mL, ig, for 1 week, respectively. At the same time, mice in group C, D, E and F were treated with carboxymethycellulose solution and 1% , 3% , 9% astragaloside in carboxymethycellulose solution (0.07, 0.2 and 0.6g/kg.d,respectively) 0.1mL, ig, for 1 week, respectively. The mice were killed and their hearts were removed after 14 day. The expression levels of CAR mRNA and protein in the myocardium were examined by RT-PCR and immunohistochemistry, respectively.Results: (1) The expression levels of myocardial CAR mRNA and protein were elevated on day 3 after virus inoculation, and reached the peack on day 7, then slowly decreased from day 15 to 30, but still sustained a high level on day 30. There were significant differences in the expression of CAR mRNA and protein between on days 3, 7,15, 30 and control group. Furthermore, the CAR protein expression levels showed significantly positive correlation with the myocardial histopathologic scores. The concentrations of serum IL-1β on days 3, 7, 15, 30 were higher markedly than those in control group, and reached the peak on day 7. The dynamic changes of IL-1β concentration were consistent with CAR expression levels and myocardial damage degree. (2) The expression levels of CAR mRNA and protein were remarkably higher in rIL-1β group than those in control group. (3) Mice in normal control group and high-dose control group had no death. However, the mortality was 45% (9/20) in myocarditic control group, 30% (6/20) in low-dose intervention group, 25% (5/20) in middle-dose intervention group and 10% (2/20) in high-dose intervention group. The mortality was significantly decreased in high-dose intervention group compared with in myocarditic control group (P<0.05), but no significant difference in low-dose, middle-dose intervention group and myocarditic control group (P>0.05). There were no any pathological leisons innormal control group and high-dose control group. The CAR mRNA and protein were low expression in the myocardium, but no significant difference in normal control group and high-dose control group (P>0.05). The expression levels of CAR mRNA and protein in myocarditic normal group were markedly higher than those in normal control group (P<0.01). After intervention of various-dose astragaloside, the expression levels of CAR mRNA and protein and myocardial histopathologic scores were significantly lower in high-dose intervention group than those in myocarditic control group (P<0.01), however, no significant difference in low-dose and high-dose intervention group compared with myocarditic normal group, respectively (P>0.05).Conclusion: The CVB3 virus infection may cause upregulation of CAR expression, and CAR expression is regulated by inflammatory mediators, such as IL-1β. Increased CAR expression may play an important role in the pathogenic mechanisms of viral myocarditis with CVB3. Astragaloside may play a pivotal role in protecting the heart injure in VMC by suppressing excessive expression of CAR.Objective: About 30% dilated cardiomyopathy (DCM) are developed from viral myocarditis (VMC), which may be due to the persistent infection of virus. The commonest viral causes of viral DCM include coxsackievirus B group (CVB) and adenovirus (ADV). Recent studies indicated that coxsackie-adenovirus receptor (CAR) plays a important role in mediating CVB or ADV attaching and subsequently internalizating with cardiac myocytes. The aim of this study was to investigate the CAR expression of myocardium with viral DCM, and its significance in the pathogenesis of viral DCM.Methods: The CVB and ADV genes were detected by RT-PCR and PCR respectively in 20 myocardium tissue specimens derived from 20 patients with end-stage DCM underwent orthotopic cardiac transplatation. These specimens were divided into coxsackievirus group (CVB positive), adenovirus group (ADV positive) and other group (CVB and ADV negative) according to the result. In addition, 5 normal donor hearts were selected as control group. The CAR mRNA and protein expression levels were assessed by RT-PCR and immunohistochemistry, respectively. The correlation between the CAR expression levels and cardiac function (ejection fraction, EF) were analyzed.Results: Viral genomes could be amplified from the myocardium of 12 of the 20 DCM patients: CVB=7, ADV=5. However, viral genomes couldn't be detected in 5 normal myocardium.Therefore, the present experiment had four groups: coxsackievirus group, adenovirus group, other group and control group. The CAR expression levels were low in control group and other group, and had an obvious increase in coxsackievirus group and adenovirus group compared with those in control group or in other group, however there was no diffference in the expression of CAR mRNA between coxsackievirus group and adenovirus group. Immunohistochemistry results showed that the CAR protein expressin levels were low, while those in coxsackievirus...
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