水飞蓟宾对心肌缺血再灌注损伤大鼠心功能和氧化应激的影响

摘要

目的 研究水飞蓟宾(silibinin,SIL)对心肌缺血再灌注损伤大鼠的心功能和氧化应激的影响.方法 将100只实验用SD大鼠随机分为假手术组,模型组和SIL低剂量[100 mg/(kg·d)]预处理组、中剂量[200 mg/(kg·d)]预处理组、高剂量[400 mg/(kg·d)]预处理组,每组各20只.SIL预处理组术前7 d开始灌胃给药.7 d后结扎大鼠冠状动脉30 min后再通建立心肌缺血再灌注损伤模型,再灌注时间为6 h.通过高分辨率超声影像系统检测舒张末期左室内径(LVIDd)和收缩末期左室内径(LVIDs)、短轴缩短率(FS)、射血分数(EF)及每搏输出量(SV);生化分析法测定血清中心肌酶含量;HE染色法观察心肌组织形态结构改变;比色法测定心肌组织中抗氧化酶活性和丙二醛(MDA)含量;Western blotting法测定心肌组织NF-κB蛋白表达;TUNEL染色法观察心肌细胞凋亡状况.结果 与模型组比较,经SIL中、高剂量预处理能够明显降低急性心肌梗死大鼠LVIDd并显著提高FS、EF和SV;可显著降低血清中心肌酶(谷草转氨酶、肌酸磷酸激酶、乳酸脱氢酶)含量,提高心肌组织中抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶)活性并显著降低MDA含量;此外,还可显著降低NF-κB蛋白表达量,并且明显改善心肌细胞凋亡状况,显著降低凋亡指数(AI),差异均具有统计学意义(P<0.05~0.01).结论 SIL具有改善心肌缺血再灌注损伤大鼠心功能并抑制其氧化应激损伤的作用,表现出对急性心肌梗死具有一定的保护作用.%Objective To study the influence of silibinin (SIL) on heart function and oxidative stress in rats with myocardial ischemia-reperfusion injury.Methods SD rats (n=100) were randomly divided into sham-operation group, model group, low-dose SIL group [100 mg/(kg·d)], mid-dose SIL group [200 mg/(kg·d)] and high-dose SIL group [400 mg/(kg·d), eachn=20]. All SIL groups were give pretreatment by oral SIL 7 d before the operation, and after 7 d the rats were given ligation of coronary artery for 30 min for establishing the model of myocardial ischemia-reperfusion injury, and the reperfusion time was for 6 h. The indexes of left ventricular end-diastolic inner diameter (LVEDd), left ventricular end-systolic diameter (LVESd), fraction shortening (FS), ejection fraction (EF) and stroke volume (SV) were detected through high resolution ultrasound imaging system. The content of serum myocardial enzyme was detected by using biochemical method, changes of histo-morphology structure were observed after HE staining, levels of antioxidase and malondialdehyde (MDA) were detected by using chromatoptometry, expression of myocardial NF-κB protein was detected by using Western blotting, and myocardial apoptosis was observed by using TUNEL method. Results Compared with model group, LVEDd decreased significantly, and FS, EF and SV increased significantly, level of myocardial enzyme (AST, CPK, LDH) was significantly reduced, activities of antioxidase (SOD, GSH-Px, CAT) were promoted, and MDA level was significantly reduced, and expression of NF-κB protein was significantly reduced, myocardial apoptosis was significantly relieved, and apoptosis index (AI) was significantly reduced (P<0.05 to P<0.01) in mid-dose SIL group and high-dose SIL group.Conclusion SIL has the effects of improving heart function and inhibiting oxidative stress damage, and plays a preventive role to acute myocardial infarction in rats with myocardial ischemia-reperfusion injury.