EPO Inhibit The Expression Of Inflammatory Factor In Rats After Myocardial Infarction Through TGF Beta1-TAK1-p38MAPK Signal Pathway

Objective:Recent studies results indicated that EPO can inhibit the expression of inflammatory factori in rats after myocardial infarction, but its mechanism is still not clear. Our previous studies show that EPO can inhibit the expression of TGF beta1in rats after myocardial infarction. together we can see that the EPO inhibits the expression of inflammatory factor may be associated with the TGF beta land its downstream signaling proteins. This experiment was designed to clear EPO in rats after myocardial infarction cytokines expression mechanisms, and whether related to TGF betal-TAK1-p38MAPK signal pathway.Methods:Through the method of threading coronary artery ligation on the left anterior descending making acute myocardial infarction rats model,58adult SD rats were divided randomly and equally into5groups:1,Sham operation group (10):only thoracotomy, thread ligation;2,Blank control group (12):only caused acute myocardial infarction the by ligation of LAD, do not give any drug treatment。3, Erythropoietin (EPO) group (12):before open chest give EPO1500U/kg subcutaneous injection, after the myocardial infarction same dose EPO subcutaneous injection twice weekly, a total of4weeks。4,EPO+MAPK Inhibitor group (12): before open chest give EPO1500U/kg+MAPK Inhibitor0.2mg/kg subcutaneous injection, after the myocardial infarction same dose EPO+MAPK Inhibitor subcutaneous injection twice weekly, a total of4weeks.5,MAPK Inhibitor group (12):before open chest give MAPK Inhibitor0.2mg/kg subcutaneous injection, after the myocardial infarction same dose EPO MAP KInhibitor subcutaneous injection twice weekly, a total of4weeks.Specimen collection:Sacrificed animal and collection heart specimens at the end of the experiment.Imrnunohistochemistry and Western blot assay for detection expression of TGF betal,TAK1,p38of MAPK, pp38of MAPK signaling pathway protein.Befor open the chest and four weeks after phlebotomize for detect expression of inflammatory factor TNF-a,IL-6,1L-1β。Results:In the process ofe experimental animal number finally enter the final analysis of make rat myocardial infarction model and experimental,14rats were dead, so the is44only. rats were sacrificed to take heart specimens28day after postoperative.Immunohistochemical method and Western blot method for determination the expression and activity change of TGF betall,TAK1,p38MAPK pp38MAPK signal pathway protein.ELISA method to measure changes of inflammatory factor TNF-a,IL-6,lL-1β。(1) The inflammatory factor activity in blood:In EPO group, EPO+SB203580group and SB203580group the inflammatory factor TNF-a,IL-6,lL-1βactivity significantly reduced (P<0.05), in which EPO+SB203580was lower most significantly, EPO group and SB203580group were not significantly different.(2) The expression of TGF betal,TAK1,p38MAPK, pp38MAPK signaling pathway protein:Compared with the control group (only causes myocardial infarction, without pharmacological intervention), In EPO group, EPO+SB203580group and SB203580group the expression of pp38MAPK protein were significantly reduced (P<0.05), EPO group and SB203580group were no significant differences (P>0.05), expression of EPO+SB203580group decreased more obviously (P<0.05).In EPO group and EPO+SB203580group TGF beta land TAK1protein decreased significantly compared with the SB203580group and control group (P<0.05), but no significant difference between the two groups (P>0.05)。Conclusion:EPO can inhibit the production of inflammation factor in rats after myocardial infarction, the mechanisms of this action may be inhibition of TGF betal-TAK1-p38MAPK signaling pathway may be one of.