Effect of atorvastatin on expression of IL-10 and TNF-alpha mRNA in myocardial ischemia-reperfusion injury in rats.
Myocardial ischemia and reperfusion (MI/R) is associated with an intense inflammatory reaction, which may lead to myocyte injury. Because statins protect the myocardium against ischemia-reperfusion injury via a mechanism unrelated to cholesterol lowering, we hypothesized that the protective effect of statins was related to the expression of TNF-alpha (TNF-alpha) and interleukin-10 (IL-10) mRNA. Seventy-two rats were randomly divided into three groups as follows: sham, I/R and I/R+atorvastatin. Atorvastatin (20 mg kg(-1)day(-1)) treatment was administered daily via oral gavage to rats for 2, 7 or 14 days. Ischemia was induced via a 30-min coronary occlusion. Reperfusion was allowed until 2, 7 or 14 days while atorvastatin treatment continued. We measured infarct size, hemodynamics and the plasma levels and the mRNA expression of TNF-alpha and IL-10 in the three groups. We demonstrated that the up-regulation of expression of both TNF-alpha mRNA and IL-10 mRNA was associated the increased plasma levels of TNF-alpha and IL-10 in the ischemic and reperfused myocardium compared with that in the sham group (P<0.01). Atorvastatin treatment prevented ischemia-reperfusion-induced up-regulation of both TNF-alpha and IL-10 mRNA, and improved left ventricular function (P<0.01). Our findings suggested that atorvastatin may attenuate MI/R and better recovery of left ventricle function following ischemia and reperfusion and IL-10 was not directly likely involved in this protective mechanism.
Sun
Yan-Ming
YM
Department of Cardiac Care Unit, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Tian
Ye
Y
Li
Xiang
X
Liu
Yuan-Yuan
YY
Wang
Lan-Feng
LF
Li
Jia
J
Li
Zhu-Qin
ZQ
Pan
Wei
W
D000818:Animals; D000069059:Atorvastatin; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006538:Heptanoic Acids / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D016276:Ventricular Function / Q000187:drug effects
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069059:Atorvastatin