右美托咪定预处理通过PI3K/Akt/mTOR信号通路对心肌缺血再灌注大鼠心脏损伤和心肌组织自噬的影响

Effects of dexmedetomidine preconditioning on cardiac injury and myocardial autophagy in rats with myocardial ischemia-reperfusion through PI3K/Akt/mTOR signaling pathway

目的:探讨右美托咪定预处理通过磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路对心肌缺血再灌注大鼠心脏损伤和心肌组织自噬的影响。方法:60只SD大鼠随机分为假手术组(n=20)、心肌缺血再灌注组(n=20)和右美托咪定预处理组(n=20),建立心肌缺血再灌注损伤模型。假手术组仅接受假手术而不造成心肌缺血,右美托咪定预处理组输注右美托咪定。比较各组大鼠心脏损伤、心肌细胞自噬、PI3K/Akt/mTOR表达、氧化应激及炎症指标。结果:与假手术组比较,右美托咪定预处理组、心肌缺血再灌注组血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平依次升高,且右美托咪定预处理组心肌梗死面积百分比明显小于心肌缺血再灌注组(均P<0.05)。与假手术组比较,右美托咪定预处理组、心肌缺血再灌注组心肌组织中LC3、Beclin、P62蛋白表达依次升高(均P<0.05)。与假手术组比较,右美托咪定预处理组、心肌缺血再灌注组心肌组织中PI3K/Akt/mTOR表达依次下降(均P<0.05)。与假手术组比较,右美托咪定预处理组、心肌缺血再灌注组血清髓过氧化物酶(MPO)、丙二醛(MDA)水平依次升高,血清超氧化物歧化酶(SOD)水平依次下降(均P<0.05)。与假手术组比较,右美托咪定预处理组、心肌缺血再灌注组血清白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平依次升高(均P<0.05)。结论:右美托咪定预处理能够保护心肌缺血再灌注损伤大鼠心脏功能,可抑制炎症因子表达、减轻氧化应激反应,其作用机制可能与下调心肌细胞自噬蛋白表达,从而激活PI3K/Akt/mTOR信号通路有关。

Objective:To investigate the effects of dexmedetomidine preconditioning on cardiac injury and myocardial autophagy in rats with myocardial ischemia-reperfusion through the PI3K/Akt/mTOR signal pathway.Methods:Sixty SD rats were randomly divided into sham operation group(n=20),myocardial ischemia reperfusion group(n=20),and dexmedetomidine preconditioning group(n=20)to establish myocardial ischemia reperfusion injury models.The sham operation group received only sham surgery without myocardial ischemia,while the dexmedetomidine preconditioning group received infusion of dexmedetomidine.Cardiac injury,cardiomyocyte autophagy,PI3K/Akt/mTOR expression,oxidative stress,and inflammatory markers were compared in each group.Results:Compared with the sham operation group,the levels of serum creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)in the dexmedetomidine preconditioning group and myocardial ischemia reperfusion group increased sequentially,and the percentage of myocardial infarction area in the dexmedetomidine preconditioning group was significantly smaller than that in the myocardial ischemia reperfusion group(all P<0.05).Compared with the sham operation group,the expression of LC3,Beclin,and P62 proteins in myocardial tissue of the dexmedetomidine preconditioning group and the myocardial ischemia reperfusion group increased sequentially(all P<0.05).Compared with the sham operation group,the expression of PI3K/Akt/mTOR in myocardial tissue of the dexmedetomidine preconditioning group and the myocardial ischemia reperfusion group decreased sequentially(all P<0.05).Compared with the sham operation group,the levels of serum myeloperoxidase(MPO)and malondialdehyde(MDA)in the dexmedetomidine preconditioning group and myocardial ischemia reperfusion group increased sequentially,while the levels of serum superoxide dismutase(SOD)decreased sequentially(all P<0.05).Compared with the sham operation group,the serum levels of interleukin-6(IL-6)and IL-1β,tumor necrosis factor-α(TNF-α)in the dexmedetomidine preconditioning group and myocardial ischemia reperfusion group were increased sequentially(all P<0.05).Conclusion:Preconditioning with dexmedetomidine can protect cardiac function in rats with myocardial ischemia-reperfusion injury,inhibit the expression of inflammatory factors,and alleviate oxidative stress reactions.The mechanism of its action may be related to downregulating the expression of autophagic proteins in myocardial cells,thereby activating the PI3K/Akt/mTOR signaling pathway.