参附注射液抗早、中期心源性休克血流动力学指标的量效关系研究

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目的研究参附注射液抗早、中期心源性休克模型大鼠的血流动力学指标量效关系。方法采用左冠状动脉前降支近心尖端、远心尖端结扎法复制早、中期心源性休克大鼠模型,分别给予休克模型大鼠0.1,0.33,1.0,3.3,10,20 ml·kg~(-1)6个剂量参附注射液(其中0.1~1.0 ml·kg~(-1)为低剂量范围,1.0~10 ml·kg~(-1)为中剂量范围,10~20 ml·kg~(-1)为高剂量范围),采用Powerlab电生理记录仪测定平均动脉压(MAP)、脉压差(PP)、ST段高度(ST Height)、左室收缩压(LVSP)、左室舒张期末压(LVEDP)、等容收缩期左心室内压力上升的最大速率(dp/dt_(max))、等容收缩期左心室内压力下降的最大速率(dp/dt_(min))等8项血流动力学相关指标,经Graph Pad Prism 6.0软件拟合量效曲线,评价参附注射液抗早、中期心源性休克模型大鼠的量效关系,计算相关剂量阈参数。结果参附注射液抗早期心源性休克模型大鼠,MAP和LVSP量效曲线呈良好的“S”型,剂量阈[D]_(20)~[D]_(80)和阈剂量[D]_(20)多集中在3.3~10 ml·kg~(-1)范围内;参附注射液抗中期心源性休克模型大鼠,MAP、ST-Height、LVSP、dp/dt_(min)和dp/dt_(max) 5项指标量效曲线呈良好的“S”型,剂量阈[D]_(20)~[D]_(80)多集中在3.3~20 ml·kg~(-1)范围内,阈剂量[D]_(20)多集中在3.3~10 ml·kg~(-1)范围内。结论参附注射液抗早、中期心源性休克模型大鼠血流动力学指标量效曲线多呈良好的“S”型,以中期模型最为明显,且其阈剂量均在3.3~10 ml·kg~(-1),提示中剂量范围为有效治疗剂量,折合成临床用量约为37.1~112 ml/人,为临床用药提供了实验依据。 Objective To study the dose-effect relationship of Shenfu injection on hemodynamics in early-stage and mid-term cardiogenic shock rats. Methods The left anterior descending coronary artery was made to approach the apical end and the distal apical ligation method was used to duplicate the model of cardiogenic shock in the early and middle stages. The rats in the shock model were given 0.1,0.33,1.0,3.3,10,20 ml · kg ~ (-1) 6 doses of Shenfu injection (0.1 ~ 1.0 ml · kg -1 for the low dose range, 1.0 ~ 10 ml · kg -1 for the medium dose range, 10 ~ 20 ml · kg -1 for high dose range). The mean arterial pressure (MAP), pulse pressure (PP), ST Height, left ventricular systolic pressure (LVSP) (Dp / dt max), left ventricular pressure drop (dp / dt min) during isovolumic systolic phase, and so on (LVEDP), the maximum rate of left ventricular pressure rise during isovolumic systole 8 hemodynamics related indicators. The dose-response curve was fitted by Graph Pad Prism 6.0 software to evaluate the dose-response relationship of Shenfu injection in anti-early and mid-term cardiogenic shock rats. The relevant dose threshold parameters were calculated. Results Shenfu injection in anti-early cardiogenic shock rat model, MAP and LVSP dose-response curves showed a good “S” type, dose threshold [D] _ (20) ~ [D] _ The dose of [D] _ (20) was mostly concentrated in the range of 3.3 ~ 10 ml · kg ~ (-1); Shenfu injection in anti-metaphase cardiogenic shock rats, MAP, ST-Height, LVSP, dp / dt_ (min) and dp / dt max (5), the dose-effect curves showed a good “S” shape and the dose threshold [D] _ (20) ~ [D] · Kg ~ (-1), the threshold dose [D] _ (20) mostly concentrated in the range of 3.3 ~ 10 ml · kg ~ (-1). Conclusion The curative effect of Shenfu injection on hemodynamics of rats with early-stage and mid-term cardiogenic shock is mostly “S ” type. The mid-term model is most obvious, and its threshold dose is in the range of 3.3-10 ml · kg ~ (-1), suggesting that the mid-dose range of effective treatment dose, equivalent to a clinical dosage of about 37.1 ~ 112 ml / person, providing experimental evidence for clinical use.
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