Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization
Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization
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DOI：
10.1007/s12013-011-9199-z
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发表时间：
2011-11-01
影响因子：
2.6
通讯作者：
Zhao, Yongxiang
中科院分区：
文献类型：
--
作者：
Li, Lang;Su, Qiang;Zhao, Yongxiang
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 caspase-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）；阿托伐他汀灌洗；洗胃控制；和 caspase-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)。阿托伐他汀组术前1周阿托伐他汀洗胃,每日1次。洗胃对照组与 NS 进行类似的洗胃。 CHO组在手术前30分钟腹腔注射（CHO：10mg/kg）。术后6 h超声心动图测定各组心脏指数。 TUNEL法和蛋白质印迹法分别用于心肌细胞凋亡和caspases-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）显着降低（P < 0.05）。此外，左心室缩短分数（FS）和心输出量（CO）也随着左心室舒张末期内径（LVEDd）的增加而减少。与CME组相比，阿托伐他汀和CHO动物心功能显着改善（P < 0.05）。与假手术组相比，心肌细胞凋亡和caspases-3/-8激活水平显着升高（P < 0.05）；与CME组相比，阿托伐他汀组和CHO组心肌细胞凋亡和caspases-3/-8激活水平显着降低（P < 0.05）。总之，阿托伐他汀预处理通过阻断心肌死亡受体介导的细胞凋亡途径抑制 CME 后心肌细胞凋亡并改善心功能。
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.