摘要
目的探讨胰岛素对大鼠急性心肌梗死(AMI)的缓解作用,评价胰岛素用药时间对缓解效果的影响,探索胰岛素通过抑制炎症作用缓解急性心肌梗死的作用机制。方法60只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备AMI模型,将大鼠随机分为4组:假手术组(n=15,仅开胸不结扎冠脉动脉左前降支)、AMI模型组(n=15,AMI模型大鼠,缺血20 min后生理盐水尾静脉滴注+皮下注射)、早期治疗组(n=15),AMI模型大鼠,缺血20 min后尾静脉胰岛素滴注+皮下注射)和晚期治疗组(n=15,AMI模型大鼠,缺血1周后尾静脉胰岛素滴注+皮下注射)。采用ELISA法分别检测大鼠模型术前、术后缺血20 min、术后缺血24 h、术后缺血48 h和术后缺血1周时血清肌酸激酶(CK)和乳酸脱氢酶(LDH)水平;超声心动图检测术后1周和4周各组大鼠左心室收缩末内径(LVESD)、左心室舒张末内径(LVEDD)、左室射血分数(EF)和缩短分数(FS);监测大鼠心脏血流动力,测定心率(HR)、左心室发展压(LVDP)、左室最大收缩和舒张末压微分(±LV dP/dtmax);伊文斯蓝(Evans Blue)染色法评估术后4周各组大鼠心肌梗死面积;ELISA检测术后4周各组大鼠血清白介素6(IL-6)和白介素17(IL-17)水平;流式细胞术评估外周血Th17占CD4+细胞比例变化。结果与假手术组相比,AMI模型组后四个时间点CK和LDH值均显著增加(P<0.05),EF、FS、LVDP和±LVdP/dtmax明显下降,LVESD、心肌梗死面积明显升高(P<0.05),血清IL-6、IL-17水平和Th17/CD4+比例显著增高(P<0.05);与AMI模型组相比,早期治疗组大鼠血清CK值和LDH值显著降低(P<0.05),且随着时间的延长差异逐渐增大;EF、FS、LVDP和±LV dP/dtmax明显升高,LVESD、心肌梗死面积明显缩小(P<0.05);血清IL-6、IL-17水平和Th17/CD4+比例显著降低(P<0.05)。晚期治疗组中与AMI模型组以上各项指标一致,未见明显急性心肌梗死后的缓解作用。结论急性心肌梗死后早期使用胰岛素可
Objective To investigate the effect and influence of insulin medication time on acute myocardial infarction,and to explore the underlying inflammatory inhibition mechanism of insulin for acute myocardial infarction.Methods AMI models were established by ligation of the left anterior descending coronary artery(LAD).Sixty male adult Sprague Dawley rats were randomly divided into four groups:sham group(n=15,open thoracotomy without ligation of left anterior descending coronary artery),saline group(n=15,AMI model rats,saline intravenous drip+subcutaneous injection after 20 min ischemia),early insulin group(n=15,AMI model rats,tail vein insulin drip+subcutaneous injection after 20 min ischemia),and late insulin group(n=15,AMI model rats,insulin drip in tail vein+subcutaneous injection 1 week after ischemia).Serum CK and LDH level were measured at different time by ELISA:before operation,ischemia for 20 min after operation,ischemia for 24 h after operation,ischemia for 48 h after operation,and ischemia for one week after operation;LV end-diastolic diameter(LVEDD)and LV end-sys-tolic diameter(LVESD),ejection fraction(EF),and fractional shortening(FS)were measured at one week and four weeks after operation by ultrasonic cardiogram;To test the rat cardiac hemodynamics,heart rate(HR),Left ventricular developed pressure(LVDP),and±LVdP/dtmax were evaluated;Evans Blue staining method was applied to assess the area of myocardial infarction at four weeks after operation.Serum IL-6 and IL-17 level were tested at four weeks after operation by ELISA.Flow cytometry was used to evaluate the Th17/CD4+cell ratio.Results Compared with the sham operation group,the values of CK and LDH increased significantly at the four time points(P<0.05),the EF,FS,LVDP,and±LVdP/dtmax decreased significantly,and the LVESD and myocardial infarction area increased significantly(P<0.05),the levels of serum IL-6,IL-17 and Th17/CD4+increased significantly in the AMI model group(P<0.05).Compared with AMI model group,CK and LDH level in early insulin group
作者
陈颖
刘冰
张廷久
CHEN Ying;LIU Bing;ZHANG Ting-jiu(Department of Cardiology,Liaoning Provincial Health Industry Group Fuxin Mine General Hospital,Fuxin Liaoning 123000,China)
出处
《临床和实验医学杂志》
2020年第11期1153-1158,共6页
Journal of Clinical and Experimental Medicine
基金
辽宁省科学技术基金资助项目(编号:201602307)。
