p38 mitogen-activated protein kinase inhibition decreases TNFalpha secretion and protects against left ventricular remodeling in rats with myocardial ischemia.
The purpose of this study was to test our hypothesis that p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 may favorably affect tumor necrosis factor alpha (TNFalpha) secretion and left ventricular (LV) remodeling after myocardial ischemia (MI). The left anterior descending coronary artery (LAD) was ligated to produce anterior MI in 40 rats that were randomly divided into two groups: p38i group (n = 24) and MIR group (MI rat models, n = 24). A sham operation group without LAD ligation (Sham, n = 16) was also studied. SB203580 (2 mg/kg) and saline was injected i.p. once every 3 days in the first two groups, respectively. One and six weeks after MI, cardiac function, myocardial fibrosis, the cardiac expressions of phosphorylated p38 MAPK (p-p38 MAPK), TNFalpha, alpha smooth muscle actin (alphaSMA) and collagen I, the ultramicrostructure of the myocardium were examined by echocardiography, histological staining, western blot, immunohistochemical staining, transmission electron microscope (TEM), respectively. Treatments with SB203580 suppressed myocardial fibrosis and LV remodeling, as well as attenuated the expressions of p-p38-MAPK, TNFalpha, alphaSMA and collagen I as compared with the MIR. In conclusion, SB203850 has an effect of inhibiting inflammation-induced fibrosis, which leads to attenuation of LV remodeling.
Yin
Huiqiu
H
Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, 250012, Shandong, People's Republic of China.
Zhang
Jidong
J
Lin
Haiqing
H
Wang
Rong
R
Qiao
Yun
Y
Wang
Bo
B
Liu
Fenye
F
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D015536:Down-Regulation; D004452:Echocardiography; D005355:Fibrosis; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008026:Ligation; D046529:Microscopy, Electron, Transmission; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000199:Actins; D024042:Collagen Type I; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C498862:Acta2 protein, rat; C093642:SB 203580