title: [Antifibrotic effects of oxymatrine in mice with chronic viral myocarditis].
abstract: OBJECTIVE
  To compare the antifibrotic effect of oxymatrine and captopril in mice with chronic viral myocarditis (CVMC) and determine the possible antifibrotic mechanism of oxymatrine in CVMC.
  
  
  METHODS
  Ninety Balb/c mice were randomly divided into normal control group 1 (n = 10), normal control group 2(n = 10) and CVMC model group (n = 70). The mice in CVMC model group were infected with coxsackievirus B(3) (CVB(3)) on days 0, 14 and 28 to establish CVMC model. The volume of CVB(3) suspension was 0.20 ml, 0.25 ml and 0.30 ml, whose 50% tissue culture infection dose was 10(9) respectively. The mice in the normal control group 1 and 2 were given normal saline of volumes equal to those of viral suspension given to the model group at the same time points. Echocardiography and collagen specific picrosirius red staining were performed to evaluate the CVMC model on day 42 for the mice of the normal control group 1 and 8 mice of CVMC model group. The remaining mice in CVMC model group were randomly divided into CVMC control group, captopril group and oxymatrine group on day 42. From then on, the mice in captopril group and oxymatrine group were treated with captopril or oxymatrine at the dose of 100 mg/kg, by gavage once a day for 28 days, and meanwhile the mice in CVMC control group and the normal control group were given equal-volume normal saline by gastric gavage every day, for 28 days successively. All these mice were sacrificed on day 70. Heart tissue slices were stained with collagen specific picrosirius red and the collagen volume fraction (CVF) was calculated with image analysis software. The expressions of AngII and TGF-beta1 were determined by immunohistochemistry and Western blotting.
  
  
  RESULTS
  Compared with normal group 1, the left ventricular end-diastolic internal diameters, left ventricular end-systolic internal diameters and heart rates were significantly increased in CVMC model group (P < 0.05, P < 0.01, P < 0.05, respectively), ejection fractions, fractional shortenings and peak velocity of aorta were all significantly decreased in CVMC model group (P < 0.01 for all comparisons), and CVF levels were significantly increased in CVMC group (P < 0.01) on day 42. Compared with normal control group 2, captopril group and oxymatrine group, CVF levels and the expressions of TGF-beta1 were significantly increased in CVMC control group (P < 0.01 for all comparisons) on day 70. The expressions of AngII in CVMC control group were higher than those in normal control group and captopril group (P < 0.01 for all comparisons), but there were no significant difference between oxymatrine group and CVMC control group (P > 0.05) on day 70.
  
  
  CONCLUSIONS
  Oxymatrine can inhibit myocardial fibrosis in CVMC, and the mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression.
authors.affiliation: Department of Pediatric Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Fang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation; D029822:Enterovirus B, Human; D005355:Fibrosis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000378:metabolism; D011807:Quinolizines / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014777:Virus Diseases / Q000473:pathology*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D002216:Captopril; D011807:Quinolizines; D053773:Transforming Growth Factor beta1; C037573:oxymatrine; D000093842:Matrines