[Myocardial inflammation and injury induced by coronary microembolization in rats: role of ERK1/2 signaling pathway].

To determine the role of extracellular signal-regulated kinases1/2 (ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of coronary microembolization (CME). The Sprague-Dawley rats were randomly divided into three groups: sham-operated group (n = 15), coronary microembolization group (n = 15) and PD98059 group (n = 15). CME model was established by injection of 42 microm microspheres 0.1 ml (3 x 10(4)/ml, 3000)into left ventricle while occluding the ascending aorta. At 30 minutes pre-operation, rats of PD98059 group were injected with PD98059 IV, a specific ERK1/2 inhibitor. Western blot and immunochemical analysis were used to determine the activation and distribution of ERK1/2. Echocardiography was employed to evaluate cardiac functions. The hematoxylin-eosin staining was used to assay myocardial inflammation. Expression of TNF-alpha and MIF mRNA was determined by RT-PCR analysis and activity of NF-kappaB assessed by electrophoretic mobility shift assay. In comparison with sham-operated group, CME increased phosphorylation of ERK1/2 (0.92 +/- 0.10 vs 0.61 +/- 0.04), local myocardial inflammatory cells (455 +/- 16 vs 47 +/- 7), expression of TNF-alpha mRNA (0.94 +/- 0.04 vs 0.60 +/- 0.09) and MIF mRNA(1.30 +/- 0.44 vs 0.63 +/- 0.25) and activity of NF-kappaB (541 +/- 25 vs 311 +/- 65) in myocardium(all P < 0.05). All of these dramatically induced cardiac dysfunction [LVEF (73 +/- 3)% vs (83 +/- 4)%, P < 0.05]. To compare with CME group, treatment of specific ERK1/2 inhibitor PD98059 blocked the activation of ERK1/2 (0.48 +/- 0.11 vs 0.92 +/- 0.10, P < 0.05), decreased inflammatory cells (401 +/- 12 vs 455 +/- 16, P < 0.05), decreased expression of TNF-alpha mRNA (0.42 +/- 0.06 vs 0.94 +/- 0.04, P < 0.05) and suppressed activity of NF-kappaB (105 +/- 14 vs 541 +/- 25, P < 0.05). Most importantly, PD98059 treatment ameliorated cardiac functions dramatically [LVEF (76 +/- 4)% vs (73 +/- 3)%, P < 0.05]. However there was no significant change in the expression of MIF mRNA (1.17 +/- 0.37 vs 1.30 +/- 0.44, P > 0.05). The present study demonstrates a novel role of ERK1/2 signaling pathway in promoting myocardial inflammation in CME. And ERK1/2 may be a novel drug target for CME therapy.