| Objetives: To discuss the mechanism of aerobic interval training activitys to improve renal inflammatory injury in rats with myocardial infarction was investigated.Methods: male Sprague Dawley rats were randomly divided into: sham-operated group(Sham),sedentary MI group(MI)and MI with AIT group(ME)(n=12).The MI model was established by ligation the left anterior descending coronary artery(LAD).Rats in Sham groups were subjected to the same surgery,but only threaded and not ligated.After surgery 1 week,rats in ME groups took adaptability training for 1 week,and then subjected to 4 weeks treadmill exercise training.The first week is adaptive training(15 m/min,30 min/d,total of 5 days).In formal training,the initial training speed is 10 m/min and the time is 10 min.Intermittent aerobic exercise was performed at a speed of 25 m/min and 7 min,followed by a 3-min interval of 15 m/min,followed by alternate exercise for a total time of 60 min.After training for 5 days a week,rats were trained continuously for 4 wk.The rats were anesthetized in abdominal cavity,hemodynamics and electrocardiogram were used to evaluate the cardiac function.Renal,serum and urine was immediately isolated and cut after death.The levels of renal MDA content,T-AOC and GSH-PX activity by Ultraviolet spectrophotometry.The activity of LDH in renal was determined by microplate assay.Primary renal inner medullary collecting duct cells(inner medullary collecting duct cells,IMCDCs)were cultured and the renal inflammatory model was established by stimulating with cluster of differentiation 40 ligand(CD40L)concentration of 1 ?g/ml for 24 h.miR-145 mimics and inhibitors were used to interfere with IMCDCs.CD40 expression in kidney and IMCDCs was detected by immunohistochemical and cytochemical staining,respectively.The levels of Trx-1 in serum and renal,NAG in serum and urine were assessed by ELISA.The expression of FoxO3 a,Bax,Bcl-2,caspase-3,cleaved-caspase-3,SIRT1,NOX2,NOX4,SOD1,SOD2,CD40,TNF-? and IL-6 protein was detected in renal by Western Blot.The expression of SIRT1 mRNA and miR-34 a was examined in renal,miR-155 and miR-145 was examined in renal and serum by RT-qPCR.Result:(1)LVEDP was significantly increased,LVSP and ądp/dtmax were significantly decreased in rats after myocardial infarction.Aerobic interval training significantly decreased LVEDP expression,significantly increased LVSP and ądp/dtmax expression.The results showed that aerobic interval training significantly improves cardiac function of rats with MI.(2)The expression of miR-155 was significantly increased,the expression of SIRT1 mRNA and protein were significantly decreased in kidney and blood of MI rats.Aerobic interval training significantly inhibited the expression of miR-155,the expression of SIRT1 mRNA and protein were significantly increased in kidney and blood of MI rats.(3)The expression of Bax protein increased,the expression of Bcl-2 protein and the ratio of Bcl-2 to Bax decreased significantly,Fox O3 a,caspase-3 and cleaved-caspase-3 proteins all increased significantly in kidney of MI rats.After aerobic interval training,Bax protein expression decreased,Bcl-2 protein expression increased,Bcl-2/Bax ratio increased,Fox O3 a,caspase-3,cleaved-caspase-3 protein all decreased significantly in kidney of MI rats.The results showed that aerobic interval training could significantly inhibit the apoptosis of renal cells after MI.(4)The expression of SIRT1 protein in kidney was negatively correlated with FoxO3 a,cleaved-caspase-3 and Bax,and positively correlated with Bcl-2.The expression of miR-155 in kidney was negatively correlated with the expression of SIRT1 protein,positively correlated with the expression of FoxO3 a,cleaved-caspase-3 and Bax,and negatively correlated with the expression of Bcl-2.(5)The expression of miR-34 a was significantly increased,SIRT1 and expression were significantly decreased,Trx-1 mRNA expression was increased,and serum Trx-1 level was increased in kidney of MI rats.Aerobic interval training could significantly inhibit local expression of miR-34 a in the kidney of MI rats,activate its downstream signaling pathway SIRT1/Trx-1,slow down the oxidative stress response of the kidney,and improve renal function.(6)The MDA content and LDH activity in the rat kidney increased significantly,the activity of T-AOC and GSH-PX decreased significantly,the expression of SOD1 and SOD2 decreased significantly,the expression of NOX2 and NOX4 increased significantly,Serum and urine NAG expression significantly increased in the kidney of MI rats.Aerobic interval training significantly reduced the MDA content and LDH activity,increased the activity of T-AOC and GSH-PX,up-regulated the expression of SIRT1,SOD1 and SOD2,inhibited the expression of NOX2 and NOX4 proteins,decreased the expression of serum and urine NAG,and improved the oxidative stress in the kidney of MI rats.(7)The expression of miR-145 in serum and kidney of MI rats was significantly decreased,and the expressions of CD40,TNF-? and IL-6 proteins were significantly increased.After aerobic interval training,the expression of serum and kidney miR-145 was significantly increased,and the expression of CD40,TNF-? and IL-6 proteins was significantly decreased.The expression of miR-145 in IMCDCs was down-regulated by CD40 L concentration and time dependence.miR-145 overexpression significantly decreased the expression of CD40,TNF-?,and IL-6 proteins in cd40l-induced IMCDCs.miR-145 gene silencing significantly up-regulated the expression of CD40,TNF-? and IL-6 proteins in IMCDCs.It is suggested that aerobic interval training may inhibit renal inflammation and improve renal function in MI rats by activating the renal miR-145/CD40 signaling pathway.Conclusion:(1)Aerobic interval training inhibited the expression of mi R-155 and activated its downstream SIRT1/Fox O3 a signaling pathway.It was suggested that aerobic interval training could significantly improve renal function in MI rats by activating the renal miR-155/SIRT1/Fox O3 a signaling pathway,inhibiting its cell apoptosis.(2)Aerobic interval training significantly inhibited local miR-34 a expression in the kidney of MI rats,activated its downstream SIRT1/Trx-1 signaling pathway,slowed down the oxidative stress response of the kidney,and improved renal function.(3)The improvement of renal function in MI rats is closely related to the up-regulation of renal miR-145 expression and the activation of the signaling pathway miR-145/CD40.It is suggested that aerobic interval training may inhibit renal inflammation and improve renal function in MI rats by activating the renal miR-145/CD40 signaling pathway. |
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