益心解毒方对心力衰竭气虚血瘀证大鼠血流动力学影响的实验研究

Effects of a compound Chinese herbal medicine Yixin Jiedu Formula on haemodynamic in rats with heart failure of qi-deficiency and blood stasis syndrome

目的:研究益心解毒方对心肌梗死后心力衰竭大鼠血流动力学与B型钠尿肽(B-type natriuretic peptide,BNP)的影响及在改善相关证候指标方面的优势。方法:利用左冠状动脉结扎术复制心肌梗死后心力衰竭大鼠模型,术后将模型大鼠随机分为模型组、益心解毒方组以及阳性药(福辛普利钠片)组,另外设假手术组对照。术后第2天,益心解毒方组给予益心解毒方中药水溶液(9.33g/kg),阳性药对照组给予福辛普利钠片剂水溶液(1.2mg/kg),模型组和假手术组分别给予等体积生理盐水,采用灌胃途径连续给药28d。观察各组动物的宏观表征变化,并记录呼吸频率,评价各组动物的血流动力学指标,并通过酶联免疫吸附法测定各组大鼠血浆中的BNP含量。结果:术后28d,益心解毒方组大鼠毛发及活动状态均优于模型组,尤其表现在大鼠足底皮肤紫暗和呼吸频率得到改善。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(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)以及平均动脉压(mean arterial pressure,MAP)明显下降(P<0.05),而益心解毒方和阳性药福辛普利钠均能很好地改善SBP和DBP,并有效地提升MAP(P<0.05)。在心室血流动力学方面,模型组大鼠的左心室收缩压(left ventricular systolic pressure,LVSP)、左室收缩压最大上升速率(maximal rate of left ventricular systolic pressure,LV+dP/dtmax)和左室舒张压最大上升速率(maximal rate of left ventricular diastolic pressure,LV-dP/dtmax)明显低于假手术组(P<0.05),益心解毒方和福辛普利钠均能上调心力衰竭大鼠的LVSP、LV+dP/dtmax和LV-dP/dtmax,进而改善心力衰竭大鼠的心室血流动力学指标(P<0.05)。酶联免疫吸附测定结果显示,模型组大鼠的血浆BNP水平明显高于假手术组(P<0.05),益心解毒方和福辛普利钠使得心力衰竭大鼠血浆BNP水平显著下降(P<0.05)。结论:益心解毒方能通过增加心力衰竭大鼠左室心肌的收缩力而上调LVSP、LV+dP/dtmax和LV-dP/dtmax,提高主动脉的SBP、DBP以及MAP,改善心肌梗死后心力衰竭大鼠血流动力学各项指标,降低心力衰竭大鼠血浆中BNP水平,说明其能够改善心力衰竭时心肌室壁压力的变化。同时,该药能够缓解心力衰竭大鼠足底皮肤的血瘀情况,提高安静状态下呼吸频率等,改善气虚血瘀证的相关表征。

OBJECTIVE： To explore the effects of Yixin Jiedu Formula （YXJDF）, a compound Chinese herbal medicine, on hemodynamic and B-type natriuretic （BNP） in a rat model of heart failure with qi deficiency and blood stasis syndrome. Moreover, its therapeutic effects in improving the symptoms were also studied. METHODS. The model of heart failure was established by ligation of left coronary artery in rats. Rats were randomly divided into sham-operated group, model group, YXJDF group and positive control （sodium fosinopril tablet） group. On the second day after the operation, rats in different groups received different treatments. Rats in the YXJDF group were treated with YXJDF （9.33 g/kg） rats in the positive control group received solution of sodium fosinopril tablet （1.2 mg/kg） and rats in the model and the control groups were given an equal volume of saline, respectively. Drugs were delivered by intragastric administration for 28 d. Symptoms such as respiratory rate and red-green-blue value of color of the plantar skin were also collected. Then hemodynamic indexes were evaluated and the levels of plasma BNP were examined by enzyme-linked immunosorbent assay （ELISA） in all groups. RESULTS： After 28 d, rats in the YXJDF group and the positive control group were more active than rats in the model group. Both YXJDF and sodium fosinopril tablet significantly improved the purple degree of the plantar skin and the respiratory rate. Compared with rats in the sham-operated group, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, and mean arterial pressure （MAP） of the model group decreased significantly （P ~ O. 05）; rats in the YXJDF group and the positive control group showed significant improvement on SBP, DBP and MAP （P^0. 05）. In ventricular hemodynamic, left ventricular systolic pressure （LVSP）, maximal rate of left ventricular systolic pressure （LV-FdP/dtmax） and maximal rate of left ventricular diastolic blood pressure （LV-dP/dtmax） of the model group were significantly down-regulated when compared with the sham-operated group （P〈0. 05）; YXJDF and sodium fosinopril tablet increased the LVSP, LV4-dP/dtmax and LV--dP/dtmax（P〈0. 05）, and thus improved ventricular hemodynamic in rats with heart failure. ELISA results showed that plasma BNP level of the model group was higher than that of the sham-operated group （P〈0.05）; YXJDF and sodium fosinopril tablet down-regulated the plasma BNP level significantly （P〈0.05） compared with the model group. CONCLUSION： YXJDF can strengthen left ventricular contractile force, increase LVSP, LV 4- dP/d tmax and LV--dP/dt SBP and SDP, and MAP, and improve hemodynamic indicators in rats with heart failure after myocardial infarction. YXJDF can also relieve the symptoms of qi deficiency and blood stasis syndrome.