摘要
目的探讨阿托伐他汀对大鼠冠状动脉微栓塞(CME)后心肌细胞凋亡及caspase-12活化的影响及意义。方法选择存活的60只大鼠随机分为假手术组、CME组、灌胃对照组、他汀组,每组15只;后3组经左心室注入微栓塞球构建CME模型;他汀组术前7d给予阿托伐他汀10mg/kg灌胃,灌胃对照组给予等量生理盐水灌胃,1次/d,连续7d。各组术后6h分别应用心脏超声检测心功能指标;TUNEL检测心肌细胞凋亡;免疫印迹法检测活化caspase-3及caspase-12的表达。结果与假手术组比较,CME组LVEF显著下降,左心室短轴缩短率和心排血量下降及左心室舒张末内径增加(P<0.05);与CME组比较,他汀组心功能明显改善(P<0.05)。与假手术组比较,CME组心肌细胞凋亡率、活化caspase-3、caspase-12含量显著增加(P<0.05),与CME组比较,他汀组心肌细胞凋亡率、活化caspase-3、caspase-12含量显著减少(P<0.05)。结论阿托伐他汀预处理治疗,可改善心功能,其机制可能是,阻断心肌细胞凋亡caspase-12介导的内质网应激凋亡途径的激活。
Objective To study the effect of atorvastatin on apoptosis of myocardiocytes and activa- tion of caspase-12 in rats following coronary microembolization (CME). Methods Sixty rats were randomly divided into CME group, sham operation group, lavage control group and atorvastatin treatment group (15 in each group). Rats in sham operation group were injected with normal sa- line before operation,those in atorvastatin treatment group were given atorvastatin (10 mg/kg a day for 7 days) ,and those in lavage control group administered the same amount of normal saline as in sham operation group. Their cardiac function was assessed by echocardiography,apoptosis of myoeardiocytes was detected by TUNEL,and expression levels of activated caspase-3 and caspase-12 were measured by Western blot 6 h after operation. Results The LVEF was significantly lower in CME group than in sham operation group (P〈0.05). The cardiac function,apoptosis of myocard- iocytes,and the activated caspase-3 and easpase-12 levels were significantly higher in atorvastatin treatment group than in CME group (P〈0. 05). However, the expression levels of activated caspase-3 and caspase-12 were significantly lower in atorvastatin treatment group than in CMF group (P〈0.05). Conclusion Atorvastatin pretreatment can significantly suppress the apoptosis of myocardiocytes following CMF and improve the cardiac function of CMF patients by blocking the activation of caspase-12.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2013年第7期748-752,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(30760262/C030313)