| Objective:To investigate the effect of aerobic exercise on the endogenous Elabela in rats with Mycardial infarct(MI)and its effect on the mechanism of cardiomyocyte proliferation.It is an effective method for the prevention and treatment of myocardial infarction and its role.Provide experimental basis.Methods:The experimental animals were 70 male SD rats aged 3 months and weighing 180-220g(purchased from Animal Experimental Management Center of Xi'an Jiaotong University,Animal Certification No:SCXK 2012-003).They randomly divided into 7 groups:sham operated group(S),sham operation+continuous aerobic exercise group(SA),myocardial infarction group(MI),myocardial infarction+continuous aerobic exercise group(MA),myocardial infarction+exogenous PBS injection group(MIP),myocardial infarction+exogenous Elabela injection group(MIE),myocardial infarction+exogenous Elabela inj ection+sustained aerobic exercise group(MIEA),and there were 10 rats in each group.The model of acute myocardial infarction was made by left anterior descending coronary artery ligation,and the aerobic exercise was carried out after 1wk of MI.The first week was adaption training(10?15m/min,30min/dx5d),the next 3wk were formal aerobic exercise training(16m/min×60min/d×5d/1wk×3wk,50%?60%VO2max.At the same time,the MIEA group and the MIE group were injected with exogenous recombinant protein Elabela(300?g/kg/d×28d).The MIP group was injected with PBS as the control group.The rats were sacrificed on the next day after finishing training,and the hemodynamics indexes were monitored.The heart and kidney were quickly removed from the abdominal aorta.The percentage of Collagen volume fraction(CVF)was observed by Masson staining,and the apoptosis was detected by Tunel method.The proliferation of myocardium and the angiogenesis were observed by immunofluorescence.The expression of Elabela,Elabela receptor APJ,Akt,p-Akt,mTOR,p-mTOR,P70 S6K,p-P70 S6K,Cyclin D1,Bcl-2,Bax,serum Elabela and kidney Elabela protein were measured by Western Blot method.Results:(1)After 8 hours of myocardial infarction,the protein expression of both Elabela in myocardiam and circulating Elabela protein were elevated.(2)The number of PCNA+ and cTnT+ double positive cells significantly increased,showing compensatory proliferation of cardiomyocytes after myocardial infarction of rats.The number of double positive cells increased significantly in exogenous Elabela group.It was suggested that exogenous recombinant protein Elabela could significantly promote myocardial cell proliferation after 28 days.(3)The results of Tunel staining showed that the expression of Tunel positive granules was significantly increased after myocardial infarction,and the number of TUNEL positive granules was significantly decreased by exogenous Elabela.Western Blot showed that the ratio of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax was significantly increased in MIE group.It indicated that myocardial infarction caused myocardial apoptosis,and exogenous recombinant protein Elabela intervention can significantly reduce myocardial cell apoptosis.(4)Immunofluorescence staining showed that the number of PCNA+ and vWF+double positive cells in the marginal area of myocardial infarction was significantly increased,and the number of PCNA+ and vWF+ double positive cells in the marginal area of myocardial infarction was significantly increased by exogenous recombinant protein Elabela for 28 days.The results showed that Elabela intervention could significantly promote myocardial angiogenesis in the marginal area of myocardial infarction.(5)Myocardial fibrosis and the percentage of myocardial collagen volume were significantly increased and cardiac function was severely impaired after myocardial infarction.The exogenous recombinant protein Elabela could significantly decrease the myocardial collagen fibers and the percentage of myocardial collagen in 28 days,and significantly improve cardiac function.These results suggest that exogenous recombinant protein Elabela can reduce myocardial fibrosis and improve cardiac function of rat heart.(6)The number of PCNA+ and cTnT+ double positive cells increased after myocardial infarction,and the proliferation of cardiomyocytes was observed.The sustained aerobic exercise could increase the number of PCNA+ and cTnT+ double positive cells and promote the proliferation and persistence of myocardial cells.The co-intervention of aerobic exercise and exogenous recombinant protein Elabela could significantly increase in myocardial PCNA+ and cTnT+ double positive cells,indicating that the promotion of myocardial infarction in the contralateral zone was much more significant.(7)Sustained aerobic exercise could significantly inhibit the apoptosis of myocardial cells in the infarcted marginal area.The effect of sustained aerobic exercise and exogenous recombinant protein Elabela was more significant on the infarcted area.(8)The number of PCNA+ and vWF+ double positive cells increased after myocardial infarction,indicating compensatory new blood vessels grew.Continuous aerobic exercise can promote the myocardial PCNA+ and vWF+ double positive cells and myocardial angiogenesis in infarcted area,and the damaged heart was repaired.The number of PCNA+ and vWF+ double positive cells in the infarcted area was more significant after continuous aerobic exercise and exogenous recombinant protein Elabela,which indicated that it was more significant to promote myocardial angiogenesis in the infarcted marginal area.(9)Sustained aerobic exercise could significantly reduce myocardial infarction in the infracted area,and improve myocardial infarction heart function.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more improvement in myocardial fibrosis and cardiac function.(10)The expression of Elabela increased after myocardial infarction.Sustained aerobic exercise or exogenous recombinant protein Elabela intervention could significantly increase the expression of myocardium Elabela.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more improvement in the increase of Elabela expression(11)The expression of circulation Elabela was elevated after myocardial infarction,Sustained aerobic exercise or exogenous recombinant protein Elabela intervention could significantly increase the level of circulating Elabela.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more improvement in the increase of serum Elabela expression.(12)MI resulted in a significant reduction in renal Elabela expression.Exogenous recombinant protein Elabela interventions significantly upregulated renal Elabela expression while sustained aerobic exercise and exogenous recombinant protein Elabela could down-regulate renal Elabela expression,which possibly associated with exercise-stimulated kidneys.The release of Elabela is probably involved in cardiac protection of myocardial infarction rats.(13)APJ and its downstream signaling pathway showed a compensatory activation.Sustained aerobic exercise or exogenous Elabela intervention could significantly increase the expression of Elabela receptor APJ and Cyclin D1 protein,and significantly increase Akt/mTOR/P70 S6K signal molecules phosphorylation level in the infarcted marginal area.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more significant effect.The expression of myocardial Elabela was positively correlated with the percentage of cardiomyocyte proliferation,positively correlated with CyclinD1,and positively correlated with downstream p-Akt/Akt.The expression of Elabela and its receptor APJ proteine increased,the downstream pathway of PI3K/Akt was activated and promoted the myocardial cells proliferated in myocardial infarction rats.Conclusions:(1)The expression of Elabela protein and the level of circulating Elabela protein were elevated after 24 hours of myocardial infarction.Exogenous recombinant protein Elabela can significantly promote cardiomyocyte proliferation,decrease myocardial apoptosis,promote myocardial angiogenesis in the marginal area of myocardial infarction,decrease myocardial fibrosis and improve cardiac function.(2)Intermittent aerobic exercise intervention can significantly improve the level of heart and circulating Elabela protein,promote myocardial cell proliferation and angiogenesis in the infarcted marginal area,inhibit cardiomyocyte apoptosis,decrease myocardial fibrosis and improve cardiac function.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more significant effect.(3)MI resulted in a significant reduction in renal Elabela expression,exogenous recombinant protein Elabela interventions significantly upregulated renal Elabela expression,whereas co-interventions of sustained aerobic exercise and exogenous recombinant protein Elabela were associated with down-regulation of renal Elabela expression,which was possibly associated with the releasing of Elabela into the blood circulation produced by exercise-stimulated kidneys,and involved in the heart protection of myocardial infarction.(4)APJ and its downstream signaling pathway showed a compensatory activation.Sustained aerobic exercise or exogenous Elabela intervention can significantly increase the protein expression of Elabela receptor APJ and Cyclin D1,and significantly increase Akt/mTOR/P70 S6K signal molecules phosphorylation level in the infarct margin area.The co-intervention of sustained aerobic exercise and exogenous recombinant protein Elabela showed a much more significant effect.It is suggested that the protein expression of Elabela and its receptor APJ were increased,its' downstream PI3K/Akt pathway was activated,and the proliferation of cardiomyocyte was promoted in the infarcted marginal area after sustained aerobic exercise. |
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