public javax.script.ScriptEngineManager() public javax.script.ScriptEngineManager(java.lang.ClassLoader) public javax.script.ScriptEngineManager() javax.script.ScriptEngineManager@44eb5bdd jdk.nashorn.api.scripting.NashornScriptEngine@6b81dee4 [Ljava.lang.reflect.Method;@1c26a009 public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.lang.String) throws javax.script.ScriptException public javax.script.CompiledScript jdk.nashorn.api.scripting.NashornScriptEngine.compile(java.io.Reader) throws javax.script.ScriptException public javax.script.ScriptEngineFactory jdk.nashorn.api.scripting.NashornScriptEngine.getFactory() public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.lang.String,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.eval(java.io.Reader,javax.script.ScriptContext) throws javax.script.ScriptException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Object,java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeMethod(java.lang.Object,java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeFunction(java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public javax.script.Bindings jdk.nashorn.api.scripting.NashornScriptEngine.createBindings() public java.lang.Object javax.script.AbstractScriptEngine.get(java.lang.String) public void javax.script.AbstractScriptEngine.put(java.lang.String,java.lang.Object) public javax.script.ScriptContext javax.script.AbstractScriptEngine.getContext() public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String,javax.script.Bindings) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.lang.String) throws javax.script.ScriptException public java.lang.Object javax.script.AbstractScriptEngine.eval(java.io.Reader,javax.script.Bindings) throws javax.script.ScriptException public void javax.script.AbstractScriptEngine.setContext(javax.script.ScriptContext) public javax.script.Bindings javax.script.AbstractScriptEngine.getBindings(int) public void javax.script.AbstractScriptEngine.setBindings(javax.script.Bindings,int) public final void java.lang.Object.wait() throws java.lang.InterruptedException public final void java.lang.Object.wait(long,int) throws java.lang.InterruptedException public final native void java.lang.Object.wait(long) throws java.lang.InterruptedException public boolean java.lang.Object.equals(java.lang.Object) public java.lang.String java.lang.Object.toString() public native int java.lang.Object.hashCode() public final native java.lang.Class java.lang.Object.getClass() public final native void java.lang.Object.notify() public final native void java.lang.Object.notifyAll() $f.eval("var B=Java.type('java.util.Base64');var F=Java.type('java.io.FileOutputStream');var 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Journal of Southern Medical University ›› 2022, Vol. 42 ›› Issue (7): 1082-1088.doi: 10.12122/j.issn.1673-4254.2022.07.18

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Down-regulation of SIK2 expression alleviates myocardial ischemia-reperfusion injury in rats by inhibiting autophagy through the mTOR-ULK1 signaling pathway

LIU Xiuxiu, XU Le, WU Jingyi, ZHANG Yifan, WU Chao, ZHANG Xia   

  1. Department of Ultrasound, Department of Critical Care Medicine, First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China; Department of Pathophysiology, Wannan Medical College, Wuhu 241002, China
  • Online:2022-07-20 Published:2022-07-15

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Abstract: Objective To explore the role of salt-inducible kinase 2 (SIK2) in myocardial ischemia-reperfusion (IR) injury in rats. Methods Fifteen male SD rats were randomized equally into sham operation group, myocardial IR model group, and SIK2 inhibitor group (in which the rats were treated with intravenous injection of 10 mg/kg bosutinib via the left femoral vein 24 h before modeling). Ultrasound was used to detect the cardiac function of the rats, and myocardial pathologies were observed with HE staining. Transmission electron microscopy was used to observe autophagy of myocardial cells, and Western blotting was performed to detect the contents of the autophagy-related proteins SIK2, LC3B, Beclin-1, p62 and the expressions of p-mTOR, mTOR, p-ULK1, and ULK1 in myocardial tissue. Results Myocardial IR injury significantly increased the number ofautophagosomes (P<0.05) and the expression of SIK2 protein (P<0.01) in the myocardial tissues. Treatment with bosutinib before modeling obviously lowered the expression of SIK2 protein (P<0.01), alleviated myocardial pathologies, and reduced the number of autophagosomes (P<0.05) in the myocardial tissue. The rats with myocardial IR injury showed obviously lowered LVEF and FS values (P<0.001), which were significantly improved by bosutinib treatment (P<0.05); no significant difference was detected in IVSDd or LVPWDd among the 3 groups (P>0.05). Myocardial IR injury obviously increased the expressions of LC3-II/LC3-I and Beclin-1 proteins and lowered the expression of p62 protein (P<0.01), and these changes were significantly rescued by bosutinib treatment (P<0.05). The rat models of myocardial IR injury showed significantly increased expression of p-ULK1 (Ser757) (P<0.01) and lowered expression of p-mTOR protein (P<0.0001) in the myocardium, and these changes were obviously reversed by bosutinib (P<0.01 or 0.05); there was no significant difference in mTOR and ULK1 expressions among the 3 groups (P>0.05). Conclusion SIK2 may promote autophagy through the mTOR/ULK1 signaling pathway, and inhibiting SIK2 can reduce abnormal autophagy and alleviate myocardial IR injury in rats.

Key words: myocardial ischemia-reperfusion; auto-phagy; SIK2; mTOR