摘要
目的:探讨布托啡诺调节脂肪酸合成酶(Fas)/脂肪酸合成酶配体(FasL)信号通路对急性心肌梗死(AMI)大鼠心肌细胞凋亡的影响。方法:126只无特定病原体(SPF)级大鼠按照随机数字表法分为空白组、AMI组、布托啡诺低剂量组(12.5μg/kg)、布托啡诺高剂量组(50.0μg/kg)、尿激酶组、rh-FasL组、布托啡诺高剂量+rh-FasL组,每组18只。除空白组外,其余组大鼠均采用结扎左冠状动脉前降支的方法复制AMI模型。建模成功1 h后,进行给药处理,每日1次,连续干预7 d。彩色多普勒超声显像仪检测大鼠左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室短轴缩短率(LVFS)、左室射血分数(LVEF)的变化;酶联免疫吸附法(ELISA)法检测大鼠血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白Ⅰ(cTnⅠ)水平;2,3,5-三苯基氯化四氮唑(TTC)染色检测大鼠心肌梗死面积百分数;苏木精-伊红(HE)染色检测大鼠心肌组织病理变化;DNA断裂的原位末端标记(TUNEL)染色检测大鼠心肌细胞凋亡;蛋白免疫印迹法(Western Blot)检测大鼠心肌组织中Bim、B淋巴细胞瘤-2基因(Bcl-2)、Fas、FasL蛋白表达。结果:与空白组比较,AMI组大鼠心肌组织病理损伤严重,LVESD、LVEDD、IL-6、TNF-α、CK-MB、cTnⅠ水平、心肌梗死面积百分数、心肌细胞凋亡率、Bim、Fas、FasL蛋白表达升高,LVFS、LVEF及Bcl-2蛋白表达降低(P<0.05);与AMI组比较,布托啡诺低剂量组、布托啡诺高剂量组、尿激酶组大鼠心肌组织病理损伤减轻,LVESD、LVEDD、IL-6、TNF-α、CK-MB、cTnⅠ水平、心肌梗死面积百分数、心肌细胞凋亡率、Bim、Fas、FasL蛋白表达降低,LVFS、LVEF及Bcl-2蛋白表达升高,rh-FasL组对应指标变化趋势与上述相反(P<0.05);与布托啡诺高剂量组比较,布托啡诺高剂量+rh-FasL组大鼠心肌组织病理损伤加剧,LVESD、LVEDD、IL-6、TNF-α、CK-MB、cTnⅠ水平、心�
Objective:To investigate the effect of butorphanol regulating fatty acid synthetase(Fas)/fatty acid synthetase ligand(FasL)signaling pathway on myocardial cell apoptosis in rats with acute myocardial infarction(AMI).Methods:Rats were grouped into blank group,AMI group,low-dose butorphanol group(12.5μg/kg),high-dose butorphanol group(50μg/kg),urokinase group(50000 U/mL),rh-FasL group(0.017 mg/kg),and high-dose butorphanol+rh-FasL group(50μg/kg+0.017 mg/kg),with 18 rats in each group.Except for the blank group,all other groups were used to establish the AMI model by ligating the anterior descending branch of the left coronary artery.After 1 hour of successful modeling,medication was administered once a day for 7 days.The changes of left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular short-axis shortening rate(LVFS),and left ventricular ejection fraction(LVEF)were detected by color Doppler ultrasonography.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),and cardiac troponinⅠ(cTnⅠ)were detected by enzyme-linked immunosorbent assay(ELISA).2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect the percentage of myocardial infarction in rats.Hematoxylin-eosin(HE)staining was used to detect pathological changes of myocardial tissue in rats.Apoptosis of rat cardiomyocytes was detected by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL).The expressions of Bim,B lymphoblastoma-2 gene(Bcl-2),Fas and FasL protein in rat myocardium were detected by Western Blot.Results:Compared with the blank group,the myocardial tissue pathological damage in the AMI group rats was severe,the LVESD,LVEDD,the levels of IL-6,TNF-α,CK-MB,cTnⅠ,the percentage of myocardial infarction area,apoptosis rate of myocardial cells,and the expression of Bim,Fas,and FasL proteins increased,the LVFS,LVEF,and the expression of Bcl-2 protein decreased(P<0.05).Compared with the AMI group,the my
作者
孟元元
刘艳
李俊
周民
陈芬
MENG Yuanyuan;LIU Yan;LI Jun;ZHOU Min;CHEN Fen(Puren Hospital Affiliated to Wuhan University of Science and Technology,Wuhan 430000,Hubei,China;Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,Hubei,China;Hubei Provincial Key Laboratory of Biological Targeted Therapy Research,Hubei 430022,Wuhan,China;Hubei Provincial Engineering Research Center for Immunodiagnosis and Treatment of Cardiovascular Diseases,Wuhan 430022,Hubei,China)
出处
《中西医结合心脑血管病杂志》
2024年第21期3892-3898,共7页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金项目(No.81300196)。
关键词
急性心肌梗死
布托啡诺
脂肪酸合成酶/脂肪酸合成酶配体信号通路
炎症
实验研究
acute myocardial infarction
butorphanol
fatty acid synthase/fatty acid synthase ligand signaling pathway
inflammation
experimental study
