Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Cell Biochem Biophys. 2011 Nov;61(2):399-406. doi: 10.1007/s12013-011-9199-z.
We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.
我们在大鼠模型中确定了阿托伐他汀对冠状动脉微栓塞（CME）后心肌细胞凋亡和半胱氨酸蛋白酶-8 激活的影响。为此，将 50 只大鼠随机均分为 CME 组、假手术（对照）组、阿托伐他汀灌胃组、胃灌洗对照组和半胱氨酸蛋白酶-8 抑制剂（CHO）组。在 CME 动物中，通过左心室注射微栓塞球。假手术动物注射生理盐水（NS）。阿托伐他汀组在手术前一周每天接受阿托伐他汀灌胃。胃灌洗对照组用 NS 进行类似灌洗。CHO 组在手术前 30 分钟腹腔注射（CHO：10mg/kg）。每组动物在术后 6 小时通过超声心动图测定心功能指数。TUNEL 检测和 Western blot 分别用于检测心肌细胞凋亡和半胱氨酸蛋白酶-3/-8 的表达。超声心动图数据显示，与假手术对照组相比，CME 组左心室射血分数（LVEF）显著降低（P < 0.05）。此外，左心室缩短分数（FS）和心输出量（CO）也降低，左心室舒张末期内径（LVEDd）增加。与 CME 组相比，阿托伐他汀和 CHO 组的心脏功能显著改善（P < 0.05）。与假手术组相比，心肌细胞凋亡和半胱氨酸蛋白酶-3/-8 的激活水平显著升高（P < 0.05）；与 CME 组相比，阿托伐他汀和 CHO 组的心肌细胞凋亡和半胱氨酸蛋白酶-3/-8 的激活水平显著降低（P < 0.05）。结论：阿托伐他汀预处理通过阻断心肌死亡受体介导的凋亡途径，抑制 CME 后心肌细胞凋亡，改善心功能。
