依托咪酯通过PI3K/AKT/eNOS信号通路抑制大鼠脑缺血再灌注后心肌损伤的研究  

Research of etomidate inhibits myocardial damage after cerebral ischemia-reperfusion in rats through PI3K/AKT/eNOS signaling pathway

作　　者：金深辉[1] 张明晓[1] 梁冬冬[1] 杜文文 黄陆平[1] JIN Shen-hui;ZHANG Ming-xiao;LIANG Dong-dong;DU Wen-wen;HUANG Lu-ping(Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,浙江温州325000

出　　处：《中国临床药理学杂志》2024年第21期3097-3101,共5页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省中医药科技计划基金资助项目(2023ZL086)。

摘　　要：目的观察依托咪酯对大鼠脑缺血再灌注后心肌损伤的影响,及其作用机制。方法将SD大鼠随机分为假手术组、模型组和低、中、高剂量实验组,每组10只。模型组和低、中、高剂量实验组均用大脑中动脉阻塞(MCAO)方法建立脑缺血再灌注模型大鼠;假手术组仅暴露大脑中动脉,但不阻塞。在建模同时,低、中、高剂量实验组分别腹腔注射5、15、25 mg·kg^(-1)依托咪酯,假手术组与模型组均腹腔注射等体积0.9%NaCl。5组大鼠每天给药1次,连续给药14 d。用酶联免疫吸附试验法检测血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)水平,用原位末端转移酶标记法检测心肌细胞凋亡率,用蛋白质印迹法检测心肌组织中蛋白激酶B(AKT)和内皮型一氧化氮合酶(eNOS)蛋白的表达水平。结果假手术组、模型组和低、中、高剂量实验组的血清LDH水平分别为(186.67±24.89)、(289.91±56.26)、(257.64±45.13)、(226.74±39.82)和(196.43±28.82)U·L^(-1),CK-MB水平分别为(17.81±3.41)、(36.89±7.75)、(31.18±6.31)、(25.21±5.88)和(19.94±4.38)U·L^(-1),心肌细胞凋亡率分别为(2.99±0.56)%、(13.51±2.37)%、(9.85±1.58)%、(5.92±0.84)%和(3.15±0.81)%,磷酸化AKT/AKT比值分别为0.12±0.02、0.24±0.04、0.39±0.06、0.52±0.07和0.97±0.08,磷酸化eNOS/eNOS比值分别为0.09±0.01、0.17±0.04、0.46±0.09、0.77±0.09和0.83±0.07。低、中、高剂量实验组和假手术组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论依托咪酯通过激活PI3K/AKT/eNOS信号通路,减轻大鼠脑缺血再灌注后心肌损伤,从而发挥保护心功能的作用。Objective To observe the effect of etomidate on myocardial damage after cerebral ischemia-reperfusion in rats and analyze the possible mechanisms.Methods The SD rats were randomly divided into sham-operation group,model group and experimental-L,-M,-H groups,with ten rats per group.The middle cerebral artery occlusion(MCAO)was used to establish cerebral ischemia-reperfusion model rats in model group and experimental-L,-M,-H groups,while the sham-operation group only exposed the middle cerebral artery,but did not block it.At the same time as modeling,experimental-L,-M,-H groups were intraperitoneally injected with 5,15 and 25 mg·kg^(-1)etomidate,respectively.The sham-operation and model groups were intraperitoneally injected with an equal volume of 0.9%NaCl.Five groups were treated for 14 d with once a day.Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)levels.Terminaldeoxynucleotidyl-transferase-mediated dUTP nick end labeling method was used to detect myocardial cell apoptosis rate.Western blotting method was used to detect the expression levels of protein kinase B(AKT)and endothelial nitric oxide synthase(eNOS)in myocardial tissue.Results The serum LDH levels of the sham-operation group,model group and experimental-L,-M,-H groups were(186.67±24.89),(289.91±56.26),(257.64±45.13),(226.74±39.82)and(196.43±28.82)U·L^(-1);the CK-MB levels were(17.81±3.41),(36.89±7.75),(31.18±6.31),(25.21±5.88)and(19.94±4.38)U·L^(-1);the cardiomyocyte apoptosis rates were(2.99±0.56)%,(13.51±2.37)%,(9.85±1.58)%,(5.92±0.84)%and(3.15±0.81)%;the phosphorylated-AKT/AKT ratios were 0.12±0.02,0.24±0.04,0.39±0.06,0.52±0.07 and 0.97±0.08;the phosphorylated-eNOS/eNOS ratios were 0.09±0.01,0.17±0.04,0.46±0.09,0.77±0.09 and 0.83±0.07.Comparing the model group with the sham-operation group,and comparing the experimental-L,-M,-H groups with the model group,the differences of the above indicators were statistically significant(all P<0.05).Conclusion

关 键 词：依托咪酯 卒中 脑缺血再灌注 心肌损伤 

分 类 号：R971.2[医药卫生—药品]