Effects Of SIK2 On Energy Metabolism In Rats With Myocardial Ischemia-Reperfusion Injury And Its Mechanism

Objective: To construct a rat myocardial ischemia-reperfusion model,and to explore the effect of salt-induced kinase 2(SIK2)on mitochondrial energy metabolism in rat myocardium and its mechanism.Methods: Adult Sprague-Dawley male rats(200-220 g)were selected to establish an acute myocardial infarction model by ligating the left anterior descending coronary artery of the rat heart.The SIK2 inhibitory group model was established by injecting Bosutinib(10 mg/kg)into the left femoral vein 24 hours before the model was established.),SIK2 inhibition group(I/R+Bosutinib)(10mg/kg treatment for24h),5 rats in each group.The myocardial ischemia of rats was detected by electrocardiogram;the changes of cardiac structure and function of rats in each group were detected by cardiac ultrasound;the pathological changes of myocardial cells of rats in each group were observed by HE staining;Changes of lactate(LA)and adenosine triphosphate(ATP)content;Western blotting(WB)detection of SIK2,p-DRP1(Ser616),DRP1,p-AKT(Ser413),AKT,p-m TOR and m TOR protein;the morphological changes of mitochondria were observed by transmission electron microscope.Results: 1.Detection of myocardial ischemia model: ECG results showed that compared with the control group,the ST segment was significantly elevated in the coronary ligation group.2.Construction and identification of the SIK2 inhibitory group model: 0mg/kg,5mg/kg,10mg/kg Bosutinib was injected into the left femoral vein to inhibit the expression of SIK2 in normal rats.And the difference was statistically significant(P<0.05).3.Myocardial histopathological changes: HE results showed that compared with Sham group,the myocardial cell pathological damage in I/R group was aggravated and the expression of SIK2 protein increased(P<0.05);compared with I/R group,I/R+Bosutinib The expression of SIK2 in the group decreased(P<0.05)and the myocardial pathological damage was alleviated.4.Changes in cardiac function and structure: the results of echocardiography showed that compared with Sham group,the left ventricular ejection fraction(LVEF)and fractional shortening(FS)of the I/R group were decreased(P<0.05);LVEF and FS were increased in I/R+Bosutinib group(P<0.05),but there was no significant difference in ventricular septum thickness(IVS)and left ventricular posterior wall thickness(LVPW)between groups(P>0.05).5.Changes in the content of ATP and lactate in myocardial tissue: The results of ELISA showed that compared with Sham,the content of ATP decreased and the content of lactate increased in the I/R group(P<0.05).The content of ATP increased and the content of lactate decreased in R+Bosutinib group(P<0.05).6.Changes of proteins related to energy metabolism in cardiac tissue: WB results showed that compared with Sham,the expression of p-DRP1(Ser616)in the I/R group was increased,and the protein expressions of p-AKT(Ser413)and p-m TOR were decreased(P<0.05);Compared with the I/R group,the protein expression of p-DRP1(Ser616)in the I/R+Bosutinib group was decreased,and the protein expression of p-AKT(Ser413)and p-m TOR was increased(P<0.05);each group AKT,t-m TOR,DRP1 protein had no significant difference(P>0.05).7.Mitochondrial ultrastructural changes in cardiomyocytes: Transmission electron microscopy showed that the morphology of Sham mitochondria was normal,the mitochondrial cristae were clear,and the overall structure of mitochondria was complete;the volume of I/R mitochondria increased,the overall mitochondria were severely swollen and vacuolated,and The internal structure of mitochondria is not shown,cristae were dissolved;mitochondrial swelling was slightly less in the I/R+Bosutinib group,and some mitochondrial cristae were unclear.Conclusion: SIK2 inhibits energy metabolism through AKT/m TOR signaling pathway and promotes mitochondrial fission.Inhibiting SIK2 and increasing energy metabolism can alleviate myocardial ischemia-reperfusion injury.