芪参益气滴丸对心衰大鼠RAAS系统的实验研究

Influence of Qishen Yiqi Gutta Pills on RAAS in rats with heart failure

目的阐明芪参益气滴丸对心梗后心衰大鼠血流动力学的改善作用及对肾素-血管紧张素-醛固酮系统(RAAS)的影响。方法利用左冠状动脉结扎术复制心梗后心衰大鼠模型,随机分为假手术组、模型组、芪参益气滴丸组以及卡托普利组。生物信号处理分析系统评价各组大鼠血流动力学参数,放免检测肾素(Ren)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)含量,Western blot检测AngⅡ的1型受体(AT1)、AngⅡ的2型受体(AT2)和血管紧张酶(ACE)的浓度变化。结果结果显示,该模型大鼠在术后28 d出现显著的心梗后心衰病理改变。在动脉血流动力学方面,与假手术组相比,模型组大鼠的收缩压(SBP)与舒张压(DBP)下降显著;此外,模型组大鼠的左室收缩压(LVSP)、左室收缩压最大上升速率(+dp/dt_(max))和舒张压最大上升速率(-dp/dt_(max))明显低于假手术组。肾素-血管紧张素-醛固酮系统(RAAS)被激活,其中伴随ACE、AT1表达的上升和AT2含量的下调。而芪参益气滴丸组和卡托普利组均能很好的改善动脉SBP和DBP(P<0.05),且2组之间无统计学差异。此外,均能上调心衰大鼠心室左室舒张压末期压(LVEDP)和-dp/dr_(max)。但在抑制RAAS激活方面,芪参益气滴丸可以下调血浆肾素-血管紧张素Ⅱ,但对醛固酮无明显作用。芪参益气滴丸能够部分抑制AT1和ACE的表达,而对AT2具有明显的上调作用。作为血管紧张素酶抑制剂,卡托普利药效主要作用在ACE和AT1上,对AT2未见显著改善作用。结论芪参益气滴丸能够改善心衰大鼠血流动力学。该机制可能通过降低肾素、AngⅡ的表达,下调ACE和AT1受体,增加保护性受体AT2的含量,进而抑制RAAS系统的激活有关。

Objective To illustrate the improving effect of Qishen Yiqi Gutta Pills on hemodynamics in rats with heart failure after myocardial infarction （MI）,and its influence on renin-angiotensin-aldosterone system （RAAS）.Methods The rat model of heart failure after MI was established by using left coronary ligation,and then the rats were randomly divided into sham-operation group,model group,Qishen Yiqi Gutta Pills group and captopril group.The hemodynamic parameters were reviewed by using biological signal processing and analysis system,the content of Ren,AngⅡ and ALD were detected by using radioimmunoassay,and level changes of AngⅡ receptors （AT1 and AT2） and ACE were detected by using Western blot method.Results The results showed that the pathological changes of heart failure after MI occurred 28 d after ligation.Compared with sham-operation group,systolic blood pressure （SBP） and diastolic blood pressure （DBP） decreased significantly,and LVSP,＋ dp/dtmax and-dp/dtmax were significantly lower in model group.RAAS were activated accompanied by the increase of ACE and AT1 and decrease of AT2.SBP and DBP were improved in Qishen Yiqi Gutta Pills group and captopril group （P 〈 0.05） and there was no statistical difference between these 2 groups.LVEDP and-dp/dtmax were up-regulated in Qishen Yiqi Gutta Pills group and captopril group,while in the aspect of inhibiting RAAS activation,Qishen Yiqi Gutta Pills down-regulated Ren and AngⅡ,but had no effect on ALD.Qishen Yiqi Gutta Pills inhibited partly the expressions of AT1 and ACE,and up-regulated significantly AT2 expression.Captopril,as an inhibitor of ACE,had effects on ACE and AT1 mainly and had no effect on AT2.Conclusion Qishen Yiqi Gutta Pills can improve the hemodynamics in rats with heart failure after MI,and the mechanism may be related to that it can inhibit RAAS activation through reducing Ren and AngⅡ,down-regulating ACE and AT1 and increasing AT2.