瑞舒伐他汀强化治疗对心肌梗死PCI术后小鼠心肌线粒体稳态的影响

目的观察瑞舒伐他汀强化治疗对心肌梗死经皮冠状动脉介入(PCI)术后小鼠心肌线粒体稳态的影响。方法选取雄性小鼠40只,随机分为假手术组、模型组、瑞舒伐他汀1组、瑞舒伐他汀2组,每组10只。假手术组与模型组在手术前1周予以5 mg/kg的蒸馏水灌胃;瑞舒伐他汀1组在手术前1周予以5 mg/kg瑞舒伐他汀灌胃;瑞舒伐他汀2组在手术前1周予以20 mg/kg瑞舒伐他汀灌胃。各组均为每日1次,共灌胃8周。观察各组血流动力学相关指标、心肌线粒体各相关标志物蛋白表达、线粒体膜电位及线粒体三磷酸腺苷(ATP)合成活力。结果与假手术组比较,模型组左心室收缩期内压(LVESP)、左心室压力上升最大速率(+dp/dtmax)水平降低,左心室压力下降最大速率(-dp/dtmax)、左心室舒张末期内压(LVEDP)水平升高,差异均有统计学意义(P<0.05)。与模型组比较,瑞舒伐他汀2组+dp/dtmax水平升高,-dp/dtmax、LVEDP水平降低,差异均有统计学意义(P<0.05);瑞舒伐他汀2组+dp/dtmax高于瑞舒伐他汀1组(P<0.05),-dp/dtmax低于瑞舒伐他汀1组(P<0.05)。与假手术组比较,模型组心肌线粒体功能学指标膜电位、ATP合成活力降低,活性氧(ROS)生成速率增加,差异均有统计学意义(P<0.05);与模型组比较,瑞舒伐他汀2组膜电位、ATP合成活力升高,ROS生成速率降低,差异均有统计学意义(P<0.05)。与假手术组比较,模型组PINK1、Beclin1、Drp1蛋白表达升高,Mfn2蛋白表达降低,差异均有统计学意义(P<0.05);与模型组比较,瑞舒伐他汀2组、瑞舒伐他汀1组PINK1、Beclin1、Mfn2蛋白表达升高,Drp1蛋白表达降低,差异均有统计学意义(P<0.05)。与假手术组比较,模型组心肌线粒体生物合成指标COXⅣ、PGC-1α、Tfam蛋白表达降低,差异均有统计学意义(P<0.05);瑞舒伐他汀2组COXⅣ、PGC-1α、Tfam蛋白表达均高于模型组(P<0.05),瑞舒伐他汀1组PGC-1α高于模型组(P<0.05);瑞舒伐他汀2组心肌线粒体生物合成指标COXⅣ、PGC-1α、Tfam蛋白表达均高于瑞舒伐他汀1组(P<0.05)。结论与5 mg/kg的瑞舒伐他汀用药方案比较,瑞舒伐他汀强化治疗心肌梗死PCI术后的心肌线粒体稳态更加具有实效性。

Effects of Intensive Rosuvastatin Therapy on Myocardial Mitochondrial Homeostasis in Myocardial Infarction Mice after PCI

Objective To investigate the effect of intensive rosuvastatin therapy on myocardial mitochondrial homeostasis in myocardial infarction mice after percutaneous transluminal coronary intervention(PCI).Methods Forty male mice were randomly divided into sham operation group,model group,rosuvastatin group 1,and rosuvastatin group 2,with 10 mice in each group.Bbefore operation,the mice in sham operation group and model group were given intragastrically 5 mg/kg distilled water,the mice in rosuvastatin group 1 were given intragastrically 5 mg/kg rosuvastatin,and the mice in rosuvastatin group 2 were intragastrically given 20 mg/kg rosuvastatin,once a day for 8 weeks.The related indexes of hemodynamics,protein expression of related markers in myocardial mitochordria mitochondrial membrane potential,and mitochondrial adenosine triphosphate(ATP)synthesis activity in each group were observed.Results Compared with sham operation group,left ventricular systolic pressure(LVESP),maximum rise speed of left ventricular pressure(+dp/dtmax)decreased,maximum drop speed of left ventricular pressure(-dp/dtmax)and left ventricular end-diastolic pressure(LVEDP)increased in model group,the differences were statistically significant(P<0.05).Compared with model group,+dp/dtmax increased,-dp/dtmax and LVEDP decreased in rosuvastatin group 2,the differences were statistically significant(P<0.05).Compared with rosuvastatin group 1,+dp/dtmax increased,-dp/dtmax in rosuvastatin group 2 decreased,the differences were statistically significant(P<0.05).Compared with sham operation group,mitochondrial membrane potential and ATP synthesis activity decreased,and reactive oxygen species(ROS)production rate in model group increased,the differences were statistically significant(P<0.05).Compared with model group,mitochondrial membrane potential and ATP synthesis activity decreased,and ROS production rate in rosuvastatin group 2 increased,the differences were statistically significant(P<0.05).Compared with sham operation group,expression levels of PINK1,Beclin1,and Drp1 proteins increased,and expression level of Mfn2 protein in model group decreased,the differences were statistically significant(P<0.05).Compared with model group,expression levels of PINK1,Beclin1,and Mfn2 proteins increased,expression level of Drp1 protein decreased,the differences were statistically significant(P<0.05).Compared with sham operation group,the expression levels ofCOXⅣ,PGC-1α,and Tfam proteins in model group decreased(P<0.05).The expression levels of COXⅣ,PGC-1α,and Tfam proteins in rosuvastatin group 2 were higher than those in model group(P<0.05),and the expression level of PGC-1αprotein in rosuvastatin group 1 was higher than that in model group(P<0.05).The COXⅣ,PGC-1α,and Tfam proteins expression levels in rosuvastatin group 2 were higher than those in rosuvastatin group 1(P<0.05).Conclusion The effect of intensive rosuvastatin treatment is better than that of 5 mg/kg rosuvastatin regimen in improving myocardial mitochondrial homeostasisis in mice with myocardial infarction after PCI.