右美托咪定对心肌缺血再灌注大鼠心肌组织自噬和SIRT1/mTOR通路蛋白的影响  

The Effects of Dexmedetomidine on Autophagy in Myocardial Tissues of Rats with Myocardial Ischemia-reperfusion and SIRT1/mTOR Pathway Proteins

作　　者：高蕤 陈思宇[1] 胡云 木开达斯·马合木提 戴晓雯[1] GAO Rui;CHEN Si-yu;HU Yun;Mukaidasi·Mahemuti;DAI Xiao-wen(Department of Anesthesiology,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,830000,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830000

出　　处：《现代生物医学进展》2024年第11期2027-2031,共5页Progress in Modern Biomedicine

基　　金：新疆维吾尔自治区自然科学基金面上项目(2019D01C324)。

摘　　要：目的:探讨右美托咪定对心肌缺血再灌注大鼠心肌组织自噬和NAD-依赖性去乙酰化酶(SIRT1)/雷帕霉素靶蛋白(mTOR)通路蛋白的影响。方法:选择45只SPF级雄性SD大鼠8周龄(平均体重220 g),随机分为假手术组、模型组和右美托咪定组,每组各15只;模型组和右美托咪定组复制心肌缺血再灌注模型,右美托咪定组造模前输注盐酸右美托咪定注射液,其他两组输注等量生理盐水。再灌注前和再灌注结束24h后检测血清心肌损伤标志物肌酸激酶同工酶(CK-MB)和肌钙蛋白I(cTnI),炎症因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α),处死大鼠后TTC染色计算心肌梗死面积百分比,qRT-PCR和Western blot法检测自噬相关蛋白微管相关蛋白1A/1B-轻链3(LC3)II/I、Beclin-1和P62蛋白,SIRT1和mTOR的表达量。结果:再灌注前模型组和右美托咪定组CK-MB、cTnI、IL-6和TNF-α水平明显高于假手术组,右美托咪定组低于模型组(P<0.05);再灌注后模型组CK-MB、cTnI、IL-6和TNF-α水平高于再灌注前,右美托咪定组低于再灌注前,且右美托咪定组显著低于模型组(P<0.05)。模型组和右美托咪定组心肌梗死面积百分比、LC3 II/I、Beclin-1和P62蛋白、SIRT1和mTOR的表达量高于假手术组,但右美托咪定组显著低于模型组(P<0.05)。结论:心肌缺血再灌注后可能进一步增加心肌损伤和炎症反应,右美托咪定预处理能够部分减轻心肌损伤、炎症反应、心肌梗死和自噬程度,可能与抑制SIRT1/mTOR信号通路活性有关。Objective:To explore the efftects of dexmedetomidine on autophagy in myocardial tissues of myocardial ischemia-reperfusion rats and NAD dependent deacetylase(SIRT1)/rapamycin target protein(mTOR)pathway proteins.Methods:45 SPF grade male SD rats of 8 weeks old(mean weight 220 g)were randomly divided into sham-surgery group,model group,and dexmedetomidine group,with 15 rats in each group;the model group and dexmedetomidine group were used to replicate myocardial ischemia-reperfusion model.The dexmedetomidine group was infused with dexmedetomidine hydrochloride injection before modeling,while the other two groups were infused with equal amount of physiological saline.Serum myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin I(cTnI),inflammatory factors interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were detected before and 24 hours after reperfusion;after euthanizing rats,TTC staining was used to calculate the percentage of myocardial infarction area.qRT-PCR and Western blot were used to detect autophagy related proteins microtubule associated protein 1A/1B light chain 3(LC3)II/I,beclin-1,and P62 proteins,SIRT1 and mTOR,too.Results:CK-MB,cTnI,IL-6,and TNF-αlevels in the model group and dexmedetomidine group before reperfusion were significantly higher than sham-surgery group,and the dexmedetomidine group was lower than model group(P<0.05);CK-MB,cTnI,IL-6,and TNF-αlevels in the model group after reperfusion were higher than before reperfusion,while the dexmedetomidine group was lower than before reperfusion,what's more,the dexmedetomidine group was significantly lower than model group(P<0.05).The percentage of myocardial infarction area,expression levels of LC3 II/I,beclin-1 and P62 proteins,SIRT1 and mTOR in the model group and dexmedetomidine group were higher than those in the sham-surgery group,but the dexmedetomidine group was significantly lower than the model group(P<0.05).Conclusion:Myocardial ischemia-reperfusion may furtherly increase myocardial injury and inflammatory respons

关 键 词：心肌缺血再灌注 自噬 右美托咪定 NAD-依赖性去乙酰化酶 雷帕霉素靶蛋白 信号通路 炎症 

分 类 号：R-33[医药卫生] R541.4R614