干预时间对福辛普利钠抗大鼠心肌重构作用的影响

目的研究干预时间对福辛普利钠抗大鼠心肌重构作用的影响机制。方法腹主动脉缩窄法复制压力负荷增高致大鼠心肌重构的动物模型,术后2 w存活动物分为假手术组(sham),手术组(AAC),手术+福辛普利钠早期干预组(Fosi-E),手术+福辛普利钠晚期干预组(Fosi-L),手术+福辛普利钠全程干预组(Fosi-W)。Mallory三色染色观察心肌组织内胶原纤维含量的变化,双抗体夹心ABC-ELISA法检测心肌组织内TNF-α和IL-10的表达。结果 Fosi-W组较早期及晚期干预组能明显降低心脏指数,减少心肌胶原容积分数,改善心功能。ELISA检测结果提示,AAC组心肌组织中TNF-α表达显著增多(P<0.01),IL-10无统计学差异,心肌组织内TNF-α/IL-10比例上调;Fosi-W组较早期及晚期干预组更能明显降低心肌组织TNF-α,显著升高IL-10在心肌组织中的表达,且能下调心肌组织TNF-α/IL-10比值(P<0.01)。结论福辛普利钠全程干预更能有效改善压力负荷增高所致大鼠心肌重构,其对TNF-α/IL-10的正向调控作用可能是其抗心肌重构的分子机制之一。

Effects of time difference intervention with fosinopril on ventricular remodeling in rats after pressure-overload

Objective To investigate the effects of time difference intervention with fosinopril on ventricular remodeling in rats after pressure-overload and its mechanism.Methods Pressure-overload was induced by abdominal aortic constriction(AAC),fosinopril(10 mg·kg-1·d-1)was administrated at early stage(Fosi-E),late stage(Fosi-L)and whole stage(Fosi-W).The expressions of TNF-αand IL-10 in myocardium were observed by enzyme linked immunosorbent assay(ELISA),collagen content in myocardium was determined by reforming Mallory staining.Results Mallory staining showed that cardiocytes arranged confused,thickening,cell spaces became obviously widen and lots of collagen could be seen in AAC group,but these phenomenon was taken a turn for the better in Fosi-W group compared with that of other operated groups;the ratio of TNF-α/IL-10 was up-regulated in myocardium of AAC group compared with that of sham group(P<0.01),but down-regulated significantly in Fosi-w groups compared with that of other operated group(P<0.01).Conclusions The effects of the whole stage intervention with fosinopril on ventricular remodeling induced by AAC are superior to those of early and late stage intervention,TNF-α/IL-10 down-regulated may be one of the molecular mechanisms.