罗氟司特对急性心肌梗死大鼠心肌损伤的影响  

Effects of roflumilast on myocardial injury in rats with acute myocardial infarction

作　　者：宋辉 徐玢[1] 郭伟[1] SONG Hui;XU Bin;GUO Wei(Department of Emergency,Beijing Tiantan Hospital Affiliated to Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京天坛医院急诊科,北京100050

出　　处：《中国临床药理学杂志》2024年第3期383-387,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 研究罗氟司特对急性心肌梗死(AMI)大鼠的治疗作用及其可能的作用机制。方法 将SD雄性大鼠随机分为假手术组、模型组(AMI)、低剂量实验组(AMI+1 mg·kg^(-1)罗氟司特)、高剂量实验组(AMI+3 mg·kg^(-1)罗氟司特),对照组(AMI+0.9 mg·kg^(-1)倍他乐克),每组10只,连续药物干预10 d后进行AMI造模。造模成功7 d后检测大鼠心功能指标水平,以酶联免疫吸附试验(ELISA)法检测血清因子水平,以试剂盒检测心肌组织氧化应激相关指标水平,以原位末端标记法(TUNEL)法检测大鼠心肌组织心肌细胞凋亡情况,以蛋白质印迹法检测心肌组织蛋白表达水平。结果 假手术组、模型组、低剂量实验组、高剂量实验组和对照组大鼠的左心室射血分数(EF)水平分别为(64.44±3.65)%、(36.12±2.50)%、(41.91±3.92)%、(49.90±2.48)%、(53.28±3.22)%,肌酸激脢同工酶(CK-MB)水平分别为(19.15±0.91)、(77.86±5.92)、(61.58±4.78)、(43.62±4.17)、(39.73±4.08)U·L^(-1),丙二醛(MDA)含量分别为(2.07±0.23)、(4.57±0.15)、(3.55±0.32)、(2.88±0.27)、(2.46±0.17)nmol·mL^(-1),TUNEL阳性细胞率分别为(3.96±0.20)%、(16.56±1.82)%、(14.30±0.80)%、(9.73±1.07)%、(7.80±0.56)%,磷酸化腺苷一磷酸活化蛋白激酶(p-AMPK)蛋白相对表达水平分别为1.10±0.09、0.34±0.04、0.59±0.06、0.87±0.05和0.78±0.09,沉默信息调节因子相关酶1(SIRT1)蛋白相对表达水平分别为0.96±0.13、0.33±0.03、0.48±0.06、0.77±0.07和0.69±0.06;模型组的上述指标与假手术组比较,低、高剂量实验组和对照组的上述指标与模型组比较,低、高剂量实验组的上述指标比较,在统计学上差异均有统计学意义(均P<0.05)。结论 罗氟司特可能通过激活AMPK/SIRT1通路抑制炎症反应和氧化应激,减轻心肌细胞凋亡改善AMI大鼠心功能。Objective To investigate the therapeutic effect of roflumilast on acute myocardial infarction(AMI) rats and its possible mechanism.Methods Sixty SD male rats were randomly divided into sham operation group,model group(AMI),experimental-L group(AMI+1 mg·kg^(-1) roflumilast),experimental-H group(AMI+3 mg·kg^(-1) roflumilast),and positive group(AMI+0.9 mg·kg^(-1) metoprolol),10 rat in each group.AMI modeling was performed after 10 days of continuous drug intervention,and cardiac function indexes of rats were detected after 7 days of successful modeling.Serum factor was detected by enzyme-linked immunosorbent assay( ELISA);myocardial tissue oxidative stress related indexes were detected by kit;myocardial cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling( TUNEL);myocardial tissue protein expression was detected by Western blot.Results The left ventricular ejection fraction( EF) levels of rats in sham operation group,model group,experimental-L group,experimental-H group and positive group were( 64.44 ± 3.65) %,( 36.12 ± 2.50) %,( 41.91 ± 3.92) %,( 49.90 ± 2.48) % and( 53.28 ± 3.22) %,respectively;creatine kinase-MB( CK-MB) levels were( 19.15 ± 0.91),( 77.86 ± 5.92),( 61.58 ± 4.78),( 43.62 ± 4.17) and( 39.73 ± 4.08) U · L^(-1),respectively;the contents of malondialdehyde( MDA) were( 2.07 ± 0.23),( 4.57 ± 0.15),( 3.55 ± 0.32),( 2.88 ± 0.27) and( 2.46 ± 0.17) nmol·mL^(-1),respectively;TUNEL positive cell rates in each group were( 3.96 ± 0.20) %,( 16.56 ± 1.82) %,( 14.30 ± 0.80) %,( 9.73 ± 1.07) % and( 7.80 ± 0.56) %;phosphorylation adenosine monophosphate-activated protein kinase( p-AMPK) protein expression levels were 1.10 ± 0.09,0.34 ± 0.04,0.59 ± 0.06,0.87 ± 0.05 and0.78 ± 0.09,respectively;silencing information regulatory factor-related enzymes 1( SIRT1) protein were0.96 ± 0.13,0.33 ± 0.03,0.48 ± 0.06,0.77 ± 0.07 and 0.69 ± 0.06,respectively.Model group compared with sham operation group;experimental-L group,experimental-H group,positive

关 键 词：罗氟司特 急性心肌梗死 氧化应激 炎症反应 腺苷酸活化蛋白激酶/沉默信息调节因子相关酶1信号通路 

分 类 号：R97[医药卫生—药品]