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Myocarditis refers to diffuse or focal inflammatory cell infiltration of the myocardial interstitium and necrosis or degeneration of adjacent myocardial fiber caused by infection or other causes,which is one of the common diseases that cause the death of infants and adolescents.Viral infection is the main pathogenic factor,but the pathogenesis of myocarditis has not yet been fully elucidated.Autophagy is a highly conservative process of self-digestion,which can provide amino acids,ATP and other substances for cells in the state of inflammation or starvation to help cells survive the energy crisis under excessive stimulation.However,excessive autophagy can promote the replication of viruses,which leads to autophagic death.In recent years,some researchers found that autophagy is closely related to the process of viral myocarditis associated with Coxsackie virus B3.The role of autophagy in the pathogenesis of myocarditis is reviewed in this article.
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Objective@#To observe the changes of LC3, lc3-Ⅱ/lc3-Ⅰ ratio, Nrf2 and Bcl2 in myocarditis induced by coxsackievirus group B type 3 (CV-B3) infection and myocardial damage in SD rats caused by particulate matter of four different pollution sources, and to further explore the mechanism of autophagy and apoptosis of myocardial cells and myocardial damage.@*Methods@#Adult SD rats were randomly divided into CV-B3 infection group (20 rats), automobile exhaust group (20 rats), coal smoke group (20 rats), burning straw group (20 rats), atmosphere group (20 rats) and control group (20 rats). The expressions of LC3, Bcl2 and Nrf2 in rats were detected by Western blot at 12 hours, 48 hours, 5 days and 10 days.@*Results@#In the first three groups of rats expression of LC3, Bcl2 and Nrf2 was upregulated, this was seen early in CV-B3 group, the peak was high, and recovery was fast; while in automobile exhaust group the above changes appeared later, the amplitude was low; in the coal smoke group rats the above changes appeared even later, but the amplitude of change was higher than that in automobile exhaust group, but lower than that of CV-B3 group. In automobile exhaust and coal smoke groups Bcl2 and Nrf2 expression was still slightly increased at day 10. After 48 hours, the above measurements in rats in the atmosphere group were temporarily up-regulated, and returned to normal on day 5. The above measurements of rats in the straw smoke and the control group did not show significant change.@*Conclusions@#In the SD rats with acute viral myocarditis induced by CV-B3 and myocardial damage induced by automobile exhaust, coal smoke and atmospheric particulate matter, the whole process of metabolism, renewal, repair and anti-damage activity of myocardial cells can be accomplished through autophagy activation, apoptosis inhibition and antioxidant mechanism.
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Objective: To investigate the effect of Shufengjiedu Capsule on the modality of myocardial tissue and levels of serum TNF-α and SAA in mice with viral myocarditis. Methods: BALB/C mice were randomly divided into normal control group, virus group, Shufengjiedu Capsule 0.1, 0.2, 0.5 g/kg/d groups, and ribavirin 0.1 g/kg/d group. The mouse model of viral myocarditis was established by ip injection of CVB3, and after 2 h of modeling, the animals were continuously admistered for 7 d. Half of the mice were killed on days 4 and 8, the myocardium tissue was HE stained to observe the pathological changes and blood samples were taken for measurement of serum TNF-α and SAA contents. Results: Compared with the control group, the pathological changes of myocardium were significantly decreased in high-dose Shufengjiedu Capsule group, and the serum TNF-α and SAA contents were significantly decreased (P < 0.05). Conclusion: Shufengjiedu Capsule has antiviral effect and could alleviate the inflammation on mice with viral myocarditis.
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Objective To study the protective effect of GYY4137 on rat myocardial cells infected by Coxsackie virus B3 (CVB3) and its signal transduction mechanism.Methods Cardiomyocytes were treated with different concentrations of GYY4137(10,50,100 μmol/L) for 24 hours before addition of 100 TCID50 CVB3 for 2 hours before serum-free conditions.After treatment,the cell viability was ascertained with Cell Counting Kit-8 (CCK-8) assay.At the same time,the levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interleukin-6 (IL-6) in the supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).Western blot was used to study the expression of nuclear factor kappa-B (NF-κB) protein and the inhibitory subunit of (IκBα) in myocardial cells.Results After exposure of cardiomyocytes to GYY4137 with different concentration (10,50,100 μmol/L)for 24 hours cell viability had no change.The NF-κB expression and the levels of TNF-α,IL-1β,IL-6 [(175.80 ± 5.05) ng/L,(25.80 ± 1.97) ng/L,(65.33 ± 3.51) ng/L] in the GYY4137-treated CVB3 infection group were significantly reduced when compared with untreated CVB3 infection group (P ＜ 0.01),respectively.Compared with the normal group,the GYY4137 concentration-dependently restrained the CVB3-mediated IκBα degradation(P ＜ 0.01).Conclusions GYY4137 exerts anti-inflammatory effects in CVB3-infected cardiomyocytes.This anti-inflammatory mechanism may be associated with suppression of the activation of the NF-κB.
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Three new glucosylated caffeoylquinic acid isomers (1-3), along with six known compounds, have been isolated from an aqueous extract of the flower buds of Lonicera japonica. Structures of the new compounds were determined by spectroscopic and chemical methods as (-)-4-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (1), (-)-3-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (2), and (-)-5-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (3), respectively. In the preliminary in vitro assays, two known compounds methyl caffeate and 2'-O-methyladenosine showed inhibitory activity against Coxsackie virus B3 with IC50 values of 3.70 μmol/L and 6.41 μmol/L and SI values of 7.8 and 12.1, respectively.
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Objective To explore the effect of HeLa cells infected with Coxsackie virus B3 (CVB3) on the changes of mTOR signal pathway under different nutritional conditions.Methods The HeLa cells were cultured under conventional culture and serum starvation culture.(1) For the conventional method,the medium with 10 g/L fetal bovine serum was added for 24 h after the Hela cells were fused into 40％ to 50％,and the medium was changed on the next day,then the virus group was infected with CVB3 of 50％ tissue culture infective dose (TCID50).However,the control group was cultured by 2 g/L fetal bovine serum.(2) For the serum starvation method,HeLa cells were cultured with the medium without fetal bovine serum for 24 h.Then the virus group was infected with CVB3 of TCID50.The cells in control group were cultured by 2 g/L fetal bovine serum.Cell morphology changes were observed by inverted microscope,and the expressions of the mTOR,p70S6K mRNA were detected with Real-time PCR at 3 h,6 h,9 h,12 h,24 h respectively in both conventional culture and serum starvation groups.Results The expressions of mTOR and p70S6K mRNA were lower in the virus group than those in control group at 12 h and the 24 h (all P ＜0.05) in the conventional culture group.And the expressions of mTOR and p70S6K mRNA in the virus group were lower than those in the control group at every time points (all P ＜ 0.05) in serum starvation group.The expressions of mTOR and p70S6K mRNA in group with serum starvation virus and the control groups were higher than those in conventional culture group in all time points,but only the expressions of mTOR mRNA were significantly different between the 2 groups (all P ＜0.05),however,the expressions of p70S6K mRNA had no significant difference between the 2 groups (all P ＞ 0.05).Conclusion CVB3 may be able to down-regulate the expressions of mTOR and p70S6K mRNA.
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Guanylate binding protein-1(GBP-1) is an interferon-induced protein. To observe its antiviral effect against Hepatitis B virus (HBV) and Coxsackie virus B3 (CVB3), we constructed an eukaryotic expression vector of human GBP-1(hGBP-1). Full-length encoding sequence of hGBP-1 was amplified by long chain RT-PCR and inserted into a pCR2.1 vector, then subcloned into a pCDNA3.1(-) vector. Recombinant hGBP-1 plasmids and pHBV1.3 carrying 1.3-fold genome of HBV were contransfected into HepG2 cells, and inhibition effect of hGBP-1 against HBV replication was observed. Hela cells transfected with recombinant hGBP-1 plasmids were challenged with CVB3, and viral yield in cultures were detected. The results indicated that recombinant eukaryotic expression plasmid of hGBP-1 was constructed successfully and the hGBP-1 gene carried in this plasmid could be efficiently expressed in HepG2 cells and Hela cells. hGBP-1 inhibit CVB3 but not HBV replication in vitro. These results demonstrate that hGBP-1 mediates an antiviral effect against CVB3 but not HBV and perhaps plays an important role in the interferon-mediated antiviral response against CVB3.
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Objective:To investigate the role of STAT3 in the pathogenesis of acute viral myocarditis(VCM)in mice and its possible mechanism.Methods:Acute VCM mice models were established forty-five mice were randomly divided into blind control group (n=10),virus-infection control group(n=15),RPMintervention group(n=20).In RPM intervention group,RPM was given to mice intraperitoneally once a day with general dosage of 0.4 mg(/kg?d)at 24 hours before infected with coxsackie virus B3,mice of virus-infection control group were given the same volume of Dulbcco's Modifed Eagle Medium and virus.Blind control group was only given the same volume of Dulbcco's Modifed Eagle Medium,but not infected coxsackie virus B3.Twelve days later,the general condition and survival rate of mice were observed and then all experimental mice were sacrificed patholog and detecting CVB3 virus titer in myocardium. And double-sandwich ELISA was used to detect the levels of IFN-?,and TNF-?in the serum.Results:The pathological changes of myocardium of the mice in RPM intervention displayed more seriously than the mice with acute VMC and both the cytokines expressions in the serum of RPM intervention group were higher than those of the acute VMC group,but there was no significant difference in the virus titer between the two groups.Conclusions:The activation of STAT3 can somehow protect myocardial tissues during the incidence of viral myocarditis in mice to inhibit its activation and improve the sensibility of mice to CVB3,although the activation of STAT3 cannot affect CVB3 virus replication,it can inhibit the over-expression of IFN-?and TNF-?to weaken myocardial damage.
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OBJECTIVE:To investigate the antiviral action of emodin in combination with other Chinese active medicine components on Coxsackie virus B3(CVB3) and explore the possible antiviral mechanism.METHODS:Hep-2 cells infected by CVB3 were cultured with different concentration and proportion of the emodin and other Chinese medicine components for 72 hours and their inhibitory effects on CVB3 replication were evaluated with cell survival rates by MTT assay.RESULTS:In the Hep-2 cell system,all the combinations between emodin and other medicine components could inhibit cytopathic effect(CPE) of CVB3-infected cells,increase cells' survival rates and decrease the cytotoxicity.The drug combination which showed the best effect of killing viruses directly was emodin:curcumine:banlangen(2:1:2),and the one showing the highest efficacy in inhibiting the replication of CVB3 in cells was emodin:curcumine:banlangen(2:0:1).CONCLUSION:The toxicity of emodin was reduced and its anti-CVB3 activity was enhanced by its combined use with other Chinese active medicine components.
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OBJECTIVE:To study the curative effects of Heart nourishing Granula on viral myocarditis(VMC)model mice.METHODS:The mice were randomly divided into treatment group and control group after intraperitoneal injected(inoculation)with a diluted solution of Coxsackie virus B 3 ,the general state and the mortality of which were observed.The blood sample and cardiac tissues of the mice were taken at different time after inoculated with virus for enzyme labeled com?pound assay,virus isolation test,light microscope test and transmission electron microscope test.RESULTS:The survival rate of the treatment group was higher than that of the control group.There was significant difference(P