芪参颗粒对后负荷加重小鼠心肌组织中Fas/Fasl凋亡信号转导通路的影响

Qishen Granule Regulated the Fas/Fasl Apoptotic Pathway in Myocardial Tissues of Mice with Transverse Aortic Constriction

目的从细胞凋亡角度探讨芪参颗粒(QSG)对后负荷加重小鼠心肌保护的作用机制。方法 40只SPF级雄性C57小鼠按体质量分为手术组(30只)和假手术组(10只),手术组利用主动脉弓缩窄术制备小鼠心肌肥厚模型,将成模后存活小鼠随机分为3组:模型组,芪参颗粒组和福辛普利组,每组10只。治疗4周后取小鼠心脏组织进行Western blot检测Fas、caspase8和cleavedcaspase3的表达,实时荧光定量PCR法检测Fas和caspase8水平。结果 Western blot结果显示:与假手术组相比,模型组的Fas、caspase8和cleaved-caspase3的表达均显著升高(P<0.05);与模型组相比,芪参颗粒组、福辛普利组可明显下调心肌肥厚小鼠心肌组织中Fas、caspase8和cleaved-caspase3(P<0.05)的蛋白表达,芪参颗粒组较福辛普利组更有优势;实时荧光定量PCR结果显示,芪参颗粒组、福辛普利组均有下调心肌肥厚小鼠心肌组织中Fas、caspase8表达的趋势,但无统计学意义(P>0.05)。结论在转录后水平调节Fas/Fasl凋亡信号转导通路相关蛋白、抑制凋亡可能是芪参颗粒发挥对后负荷加重小鼠心肌保护作用的重要机制之一。

Objective To explore the mechanism of Qishen granule（QSG）on the myocardial protection in mice with transverse aortic constriction（TAC）.Methods Forty SPF grade male C57 mice were divided into operation group（n =30）and sham operation group（n =10）according to the body mass.Mice in the operation group were prepared by transverse aortic constriction to induce cardiac hypertrophy,and then were randomly divided into model group（n =10）,QSG group（n =10）and fosinopril group（n =10）.After 4 weeks of treatment according to group,the left ventricular was collected.Subsequently,the protein of Fas,caspase 8 and cleaved-caspase 3 were analyzed by western-blot while the mRNA expression of Fas and caspase 8 were tested by real-time fluorescence quantitative PCR.Results Protein expression of Fas caspase 8 and cleaved-caspase 3increased dramatically in model group comparing to sham group（P 〈0.05）.Compared with model group,the protein expression of Fas,caspase 8 and cleaved-caspase 3 decreased in QSG group and fosinopril group（P 〈0.05）,which was lower in QSG group than that in fosinopril group.The result of real-time fluorescence quantitative PCR showed that the the mRNA expression of Fas and caspase 8in the myocardium of myocardium was decreased,but there was no significant difference（P 〉0.05）.Conclusion QSG regulated moleculars in Fas/Fasl apoptotic pathway at their post-transcription stage and then decreased apoptosis in myocardial tissue with hypertrophy.