The effects of NK4 on viral myocarditis mice.
NK4 may be a promising agent to inhibit tumor invasion and metastasis. To observe the effects of NK4 on the cardiovascular system with pathological injury and to discuss the mechanism, we established an experimental model of viral myocarditis (VCM) by coxsackievirus B3 infection in Balb/c mice on Day 0 and administered NK4 twice daily to the VCM and control mice from Day 20 to Day 45. We then evaluated the cardiac function by means of ultrasonic inspection. Hepatocyte growth factor, TNF (tumor necrosis factor)-alpha, and angiotensin II levels in the myocardial tissue were measured with enzyme-linked immunosorbent assay. Myocardium histopathology was examined with hematoxylin and eosin stain. Collagen deposition of the myocardium was detected through Masson staining. Microvessel staining with the RECA antibody and apoptosis detection with terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling were performed in the myocardium. The changes in MMP3 (matrix metalloproteinase 3), MMP9, TIMP1 (tissue inhibitor of metalloproteinase 1), and TGF (transforming growth factor)-beta1 expression in the myocardium were measured by reverse-transcriptase polymerase chain reaction. We found that NK4 intervention increased TGF-beta and angiotensin II expression, suppressed MMPs, improved the activities of TIMPs, and then promoted collagen deposition in the myocardium. NK4 intervention also decreased the microvessels' density and increased the apoptotic cell count in the myocardia of VCM mice. However, we did not observe the obvious changes in the myocardia of control mice after NK4 intervention. These data suggest that NK4 made negative impacts on the restoration of cardiac function and the recovery from VCM in the experimental mice.
Shen
Difei
D
Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, P.R. China.
Tang
Qizhu
Q
Huang
Zhengrong
Z
Chen
Ying
Y
Xiong
Ran
R
Wu
Hui
H
Huang
Ji
J
Feng
Siting
S
Yan
Ling
L
Bian
Zhouyan
Z
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D017228:Hepatocyte Growth Factor; D020782:Matrix Metalloproteinases