The cardioprotective effect of fluvastatin on ischemic injury via down-regulation of toll-like receptor 4.
To determine whether the cardioprotection effect of fluvastatin mediates by toll-like receptor 4 (TLR4) signaling pathway, fifty Sprague-Dawley rats were randomly divided into five groups: sham operation group, ischemia/reperfusion (I/R) group, fluvastatin groups (high-dosage, medium-dosage, low-dosage, n = 10 in each group). Except sham operation group, the rest four groups of rats were artificially afflicted with coronary occlusion for 30 min, then reperfusion 2 h. Light microscope and transmission electronic microscope were used to observe structural changes of myocardium. RT-PCR was used to measure TLR4 mRNA expression level, TLR4 protein expression was detected by immunohistochemistry. Western blot was used to measure myocardial NF-κB protein level; ELISA was used to measure the level of TNF-α in myocardium. The results demonstrated that fluvastatin treatment markedly decreased ischemic injury caused by ischemia/reperfusion, and inhibited the expression levels of TLR4, TNF-α and NF-κB, all of which up-regulated by ischemia/reperfusion. Taken together, our results suggest that proper dosage of fluvastatin may have protective effect on the ischemic injury mediated by ischemia/reperfusion in the hearts, which might be associated with inhibition of TLR4 signaling pathway and inflammatory response during ischemia/reperfusion.
Yang
Jun
J
Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, 443000 Yichang, Hubei Province, China.
Zhang
Xiao-Dong
XD
Yang
Jian
J
Ding
Jia-Wang
JW
Liu
Zhao-Qi
ZQ
Li
Shu-Guo
SG
Yang
Rui
R
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D000077340:Fluvastatin; D006321:Heart / Q000187:drug effects / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002316:Cardiotonic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000077340:Fluvastatin