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1、科素亚对心力衰竭大鼠心肌细胞凋亡及Bax、Bcl-2蛋白表达的影响【摘要】目的应用科素亚治疗慢性压力负荷性心力衰竭大鼠,探讨其对心肌细胞凋亡及Bax、Bcl-2蛋白表达水平的影响,为心力衰竭发病机制及治疗提供实验依据。方法30只SD大鼠随机分为心衰组(n=10)、治疗组(n=10)和对照组(n=10),采用鼠腹主动脉缩窄术复制心力衰竭模型。治疗组给予科素亚30mg·kg-1·d-1灌胃,心衰组和对照组分别给予等体积生理盐水灌胃;3个月后测量血流动力学指标,原位脱氧核糖核酸酶末端标记法(TUNEL)检测心肌细胞凋亡,免疫组织化学染色法检测心肌Bax、Bcl-2
2、蛋白表达。结果心衰组与对照组相比,心功能明显减退(P<0.01),心肌细胞凋亡指数明显增加(P<0.01),心肌细胞中Bcl-2蛋白表达减少、Bax蛋白表达增加、Bcl-2/Bax比值降低;治疗组与心衰组相比,心室重构改善(P<0.05),心肌细胞凋亡减少(P<0.01),心肌细胞中Bcl-2表达增加、Bax表达减少(P<0.05)。结论心力衰竭大鼠心肌细胞凋亡增加与Bcl-2蛋白表达降低、Bax蛋白表达增加有关。减少Bax蛋白表达,同时增加Bcl-2蛋白表达水平,从而抑制心肌细胞凋亡改善心功能,是科素亚治疗心力衰竭的重要机制之
3、一。【关键词】心力衰竭心肌细胞凋亡Bcl-2科素亚Abstract:ObjectiveTostudytheeffectsofcozaartherapyonmyocardialapoptosisandexpressionsofproapoptoticproteinBaxandantiapoptoticproteinBcl-2inratswithchronic10pressureoverloadheartfailure(CHF),anditsmechanisms.Methods30ratswererandomlydividedintothreegroups:CH
4、Fgroup,treatmentgroupandshamoperationcontrolgroup(n=10each).TheratmodelofCHFwasinducedbyapplyingtransverseabdominalaorticconstriction.Treatmentwasstarted6weeksafterthesurgery,withcozaar30mg/kgp.o.q.d.forthemodelratsintreatmentgroup,andwithNSfortheother2groups.Bytheendof3months,theh
5、emodynamicparametersweredetermined,beforetheratswerekilledtoremovetheheart.Theheartsweredissectedandweighed,theapoptosiswasassessedbyusingTUNELmethod,theexpressionsofBax,andBcl-2weredeterminedbyimmunohistochemistryandimageanalysis.ResultsAscomparedwiththecontrolgroup,themodelratsin
6、CHFgroupshowedsignificantsystolicdysfunction(P<0.01),increasedmyocardialapoptosis(P<0.01),andelevatedexpressionofBaxandreducedexpressionofBcl-2.WhentheresultswerecomparedbetweenthetreatmentandCHFgroups,itwasfoundthatcozaartreatmentresultedin:improvedleftventricularremodeling(
7、P<0.05);reducedmyocardialapoptosis(P<0.01),anddecreasedBaxexpressionandincreasedBcl-2expressioninmyocardium(P<0.05).ConclusionThedatashowthatinCHF,theincreaseofmycardialapoptosisisrelatedto10theelevationofBaxexpressionandreductionofBcl-2expression,whilecozaarcanamelioratet
8、hesystolicdysfunctionandre