Etanercept attenuates myocardial ischemia/reperfusion injury by decreasing inflammation and oxidative stress.

The protective role of etanercept in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether etanercept modulates neutrophil accumulation, TNF-α induction and oxidative stress in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, MI/R+ etanercept. The results demonstrated that compared to MI/R, etanercept reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels, and both serum and myocardial TNF-α production. Etanercept also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. In summary, our data suggested that etanercept has protective effects against MI/R injury in rats, which may be attributed to attenuating inflammation and oxidative stress

Effect of etanercept on cardiomyocyte apoptosis induced by MI/R.

<p>(A) TUNEL staining. (B) Quantitative analysis of percentage of cardiomyocyte apoptosis. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

Effect of etanercept on TLR4 gene expression in the ischemia area in the heart subjected to MI/R.

<p>Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

Effect of etanercept on NF-κB expression in the ischemia area in the heart subjected to MI/R.

<p>(A) Representative immunoblots of samples from rat ventricles subjected to different treatment groups. (B) Quantitative densitometric analysis of NF-κB protein with β-actin as an internal standard. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

Effect of etanercept on cardiac function.

<p>(A) The effect of etanercept on LVEF. (B) The effect of etanercept on LVEDP. (C) The effect of etanercept on –dp/dx max. (D) The effect of etanercept on +dp/dx max. LVEF, left ventricle ejection fraction; LVEDP, left ventricle end-diastolic pressure. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.01 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

Etanercept ameliorates oxidative stress after myocardial ischemia/reperfusion injury.

<p>Etanercept significantly decreased (A) the content of malondialdehyde (MDA) and (B) enhanced superoxide dismutase (SOD); and (C) glutathione peroxidase (GSH-PX) activities in ischemia reperfusion rats’ heart. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

The comparison of LDH activity in each group.

<p>The LDH activity in the sham group was relatively lower, while the LDH activity in MI/R group was significantly increased, which was inhibited by etanercept. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

Immunohistochemical analysis of myocardial TLR4 expression.

<p>TLR4 is brown staining. Sham, sham group; MI/R, MI/R group; MI/R+Eta, MI/R+ etanercept group. Data were expressed as mean ± SD (n = 10 in each group).*<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p

The comparison of MPO activity in each group.

<p>The MPO activity in the sham group was relatively lower, while the MPO activity in MI/R group was significantly increased, which was blocked by etanercept. Data were expressed as mean ± SD (n = 10 in each group). *<i>P</i><0.05 versus the sham group, ^#<i>P</i><0.05 versus MI/R group.</p