中文摘要：

目的研究参附注射液（Shenfu Injection,SFI）抗早、中期心源性休克模型大鼠的微循环效应指标量效关系。方法采用左冠状动脉前降支近心尖端、远心尖端结扎的方法复制早、中期心源性休克大鼠模型,分别给予休克模型大鼠0.1,0.33,1.0,3.3,10,15,20 m L·kg-1共7个剂量SFI（其中0.1-1.0 m L·kg-1为低剂量范围,1.0-10 m L·kg-1为中剂量范围,10-20 m L·kg-1为高剂量范围）,用Geneandi-M2型倒置微循环系统观察假手术组,早、中期模型组,早、中期给药组大鼠给药后60 min的红细胞流速、微血管管径、白细胞黏附数及微血管通透性。经Graph Pad Prism 6.0软件拟合量效曲线,评价SFI抗早、中期心源性休克模型大鼠的微循环量效关系,计算相关剂量阈参数。结果 10 m L·kg-1以上剂量的SFI可使早期休克大鼠微血管管径变宽、白细胞黏附数减少,但对红细胞流速和微血管通透性未见明显改善。其中,微血管管径量效曲线呈良好的＂S＂型,最佳剂量阀范围：[D]20-[D]80=（4.03-9.14）m L·kg-1,中位剂量：[D]50=6.07 m L·kg-1,阈剂量：[D]20=4.03m L·kg-1;10 m L·kg-1以上剂量的SFI可使中期休克大鼠红细胞流速加快、白细胞黏附数减少,且量效曲线均呈良好的＂S＂型,但对微血管通透性和微血管管径未见明显改善。其中,红细胞流速最佳剂量阀范围：[D]20-[D]80=（6.85-15.28）m L·kg-1,中位剂量：[D]50=10.23 m L·kg-1,阈剂量：[D]20=6.85 m L·kg-1,白细胞黏附数最佳剂量阀范围：[D]20-[D]80=（5.57-5.86）m L·kg-1,中位剂量：[D]50=5.72 m L·kg-1,阈剂量：[D]20=5.57 m L·kg-1。结论本研究中量效曲线呈良好的＂S＂型的微循环指标,其阈剂量均在4.03-6.85 m L·kg-1,提示中剂量为有效剂量范围,折合成临床用量约为44.8-77.0 m L·d-1,为临床用药提供实验依据。

英文摘要：

Objective To observe the dose-effect relationship of Shenfu Injection（SFI） with the microcirculatory indexes of early- and mid-stage cardiogenic shock rats. Methods The rat model of early- and mid-stage of cardiogenic shock was established by ligating the ending or root of left anterior descending coronary arteries（LADCA）.The rat microcirculation indexes including flow rate of RBC in microvessel, diameters of microvessel, leukocyte adhesion count, and vascular permeability which calculated by FITC-dextran leakage were observed 60 min after medication under an Geneandi-M2 inverted intravital microscope and with a high-speed video camera system after intravenous administration of 0.1,0.33,1.0,3.3,10,15,20 m L·kg-1SFI（low dosage range：0.1-1.0 m L·kg-1,middle dosage range：1.0-10 m L·kg-1,high dosage range：10-20 m L·kg-1）. After fitting dose-response curves with Graph Pad Prism 6.0 software,we evaluated the dose-response relationship of SFI with the microcirculatory indexes of early- and mid-stage cardiogenic shock rats and calculated the relevant dose-threshold parameters. Results SFI in the dosage over 10 m L·kg-1broadened the microvessel diameter and decreased leukocyte adhesion count of early cardiogenic shock rats, but had no obvious effect on improving the RBC flow rate or vascular permeability. The dose-effect curve for microvessel diameter was in well ＂S＂ shape, and the effective dose range was [D]20- [D]80=（4.03-9.14）m L·kg-1,median dose was [D]50=6.07 m L·kg-1,and threshold dose was[D]20=4.03 m L·kg-1. SFI in the dosage over 10 m L·kg-1increased RBC flow rate and decreased leukocyte adhesion count of mid-stage cardiogenic shock rats,but had no obvious effect on vascular permeability or microvessel diameter. The dose-effect curves for RBC flow rate and leukocyte adhesion count were in well ＂S＂ shape. The effective dose range for RBC flow rate was [D]20-[D]80=（6.85-15.28）m L·kg-1, median dose was [D]50=10.23 m L·kg-1, and threshold dose was [D]20=6.85 m L·kg-1. The