依托咪酯调节AMPK/NLRP3信号通路对急性心肌梗死大鼠心肌损伤的影响

Effect of etomidate on myocardial injury in rats with acute myocardial infarction by regulating the AMPK/NLRP3 signaling pathway

目的探究依托咪酯调节腺苷酸活化蛋白激酶(AMPK)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法取SD大鼠通过结扎左冠状动脉前降支建立AMI模型,随机分为模型组、依托咪酯组、Dorsomorphin组、依托咪酯+Dorsomorphin组,每组12只,另取12只大鼠作为假手术组开胸后不结扎,分组处理后检测各组大鼠心功能、心肌组织病理损伤及纤维化、血清乳酸脱氢酶(LDH)、肌酸磷酸激酶(CPK)、白细胞介素(IL)-1β、IL-6、超氧化物歧化酶(SOD)与丙二醛(MDA)水平、心肌组织IL-1β、IL-6、SOD与MDA水平、心肌组织AMPK/NLRP3通路相关蛋白表达。结果与假手术组相比,模型组大鼠心肌组织呈严重病理损伤,左室舒张末期内径(LVDD)、左室收缩末期内径(LVDS)、心肌胶原容积分数(CVF)、血清LDH、CPK、IL-1β及IL-6水平、心肌组织IL-1β、IL-6及MDA水平、心肌组织NLRP3蛋白表达明显升高(P<0.05),左室射血分数(EF)、血清及心肌组织SOD水平、心肌组织p-AMPK/AMPK明显降低(P<0.05)。与模型组相比,依托咪酯组大鼠心肌组织病理损伤减轻,LVDD、LVDS、心肌CVF、血清LDH、CPK、IL-1β及IL-6水平、心肌组织IL-1β、IL-6及MDA水平、心肌组织NLRP3蛋白表达均降低(P<0.05),EF、血清及心肌组织SOD水平、心肌组织p-AMPK/AMPK升高(P<0.05);Dorsomorphin组大鼠各指标变化趋势与依托咪酯组相反,且Dorsomorphin可减弱依托咪酯对模型组大鼠各指标的作用。结论依托咪酯可通过调控AMPK/NLRP3信号传导而抑制AMI后炎症与氧化应激反应,进而减轻AMI大鼠心肌组织损伤及纤维化,改善其心功能。

Objective To investigate the effect of etomidate on myocardial injury in acute myocardial infarction(AMI)rats by regulating the adenosine monophosphate activated protein kinase(AMPK)/nucleotide binding oligomeric domain-like receptor protein 3(NLRP3)signaling pathway.Methods The AMI model was established in SD rats by ligating the anterior descending branch of the left coronary artery,and the SD rats were randomly grouped into model group,etomidate group,Dorsomorphin group,and etomidate+Dorsomorphin group,with 12 rats in each group,another 12 rats were selected as the sham operation group without ligation after thoracotomy.After grouping and treating,the cardiac fraction,the pathological damage and fibrosis in myocardial tissue,the levels of serum lactate dehydrogenase(LDH),creatine phosphokinase(CPK),IL-1β,IL-6,superoxide dismutase(SOD)and malondialdehyde(MDA),the levels of IL-1β,IL-6,SOD and MDA in myocardial tissue,the expression of AMPK/NLRP3 pathway related proteins in myocardial tissue of rats were measured.Results Compared with the sham surgery group,the myocardial tissue of rats in the model group showed severe pathological damage.The left ventricular end diastolic diameter(LVDD),left ventricular end systolic diameter(LVDS),myocardial collagen volume fraction(CVF),levels of serum LDH,CPK,IL-1βand IL-6,levels of IL-1β,IL-6 and MDA in myocardial tissue,and protein expression of NLRP3 in myocardial tissue were obviously increased(P<0.05).The EF,levels of SOD in serum and myocardial tissue,and p-AMPK/AMPK in myocardial tissue were obviously reduced(P<0.05).Compared with the model group,the pathological damage of myocardial tissue in the etomidate group was reduced.The LVDD,LVDS,myocardial CVF,levels of serum LDH,CPK,IL-1βand IL-6,levels of IL-1β,IL-6 and MDA in myocardial tissue,and protein expression of NLRP3 in myocardial tissue were obviously reduced(P<0.05).The EF,levels of SOD in serum and myocardial tissue,and p-AMPK/AMPK in myocardial tissue were obviously increased(P<0.05).The changes of various indicators in the Dorsomorphin group rats were opposite to that of the etomidate group,and Dorsomorphin weakened the effect of etomidate on various indicators of the model group rats.Conclusion Etomidate can inhibit inflammation and oxidative stress response after AMI by promoting AMPK/NLRP3 signaling,thereby reducing myocardial tissue damage and fibrosis in AMI rats and improving their cardiac function.