学术论文

      参附注射液改善早、中期心源性休克大鼠血液粘度量效关系研究

      Dose-Effect Relationship of Shen Fu Injection (SFI) Between Blood Viscosity and the Early-and Mid-Stage Cardiogenic Shock in Rats

      摘要:
      目的:本文旨在研究参附注射液(Shen Fu Injection,SFI)改善早、中期心源性休克模型大鼠的血液粘度量效关系.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0.10、0.33、1.00、3.30、10.00、20.00 mL·kg-1 6个剂量SFI(其中0.1-1.0 mL·kg-1为低剂量范围,1.0-10.0 mL·kg-1为中剂量范围,10-20 mL·kg-1为高剂量范围),采用血液流变仪测定给药后60 min全血粘度(低切、中切、高切)、血浆粘度等4项血液流变学相关指标,经GraphPad Prism 6.0软件拟合量效曲线,评价参附注射液改善早、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:10 mL·kg-1 SFI可改善早期休克大鼠血液粘度指标,且全血粘度低切(10/s)、中切(60/s)、高切(150/s)3项指标量效曲线呈良好的“S”型,剂量阈[D]20-[D]80和阈剂量[D]20多集中在3.3-6.3 mL·kg-1范围内;10、20 mL· kg-1SFI均可改善中期休克大鼠血液粘度指标,且4项指标量效曲线均呈良好的“S”型,剂量阈[D]2o-[D]80和阈剂量[D]20多集中在3.3-10.0 mL·kg-1范围内.结论:SFI改善早、中期心源性休克模型大鼠血液粘度指标量效曲线多呈良好的“S”型,且其阈剂量均在3.3-10.0 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37.1-112.0 mL/人,为临床用药提供了实验依据.
      Abstract:
      This study aimed at investigating the dose-effect relationship of SFI between the blood viscosity and the early-and mid-stage cardiogenic shock and the mediatory effect on rats.The end or root of left anterior descending coronary arteries (LADCA) was ligatured to establish the rat model of the early-and mid-stage cardiogenic shock.The blood viscosity indexes included low shear rate (LSR,10/s),middle shear rate (MSR,60/s),high shear rate (HSR,150/s) of the whole blood viscosity and plasma viscosity (PV),being observed 60 mins after the venous administration of 0.10,0.33,1.00,3.30,10.00 and 20.00 mL·kg-1 SFI (low dosage range:0.1-1.0 mL·kg-1,middle dosage range:1.0-10 mL·kg-1,high dosage range:10-20 mL·kg-1) with a blood rheometer.Dose-response curves were fitted by GraphPad Prism 6.0 software,the dose-response relationship of SFI between the blood viscosity and the early-and mid-stage cardiogenic shock in rats was evaluated to calculate the dose threshold parameters of the indexes.It was found that the blood viscosity indexes were improved with the dosage of 10 mL·kg-1 SFI in rats with the early-stage cardiogenic shock,while the dose-response curves of LSR,MSR and HSR at the early stage all presented favorable "s" shapes.Most of the effective dose range [D]2o-[D]80 and the threshold dose [D]20 were between 3.3 and 6.3 mL· kg-1.The four indexes of blood viscosity were improved with the administration of 10 and 20 mL·kg-1 SFI in mid-stage model rats with favorable "s" shapes in the dose-response curves.Most of the effective dose range and the threshold dose were in the range of 3.3 to 10.0 mL·kg-1.In conclusion,most of the dose-response curves of blood viscosity indexes in early-and mid-stage cardiogenic shock rats presented favorable "s" shapes with the threshold dose between 3.3 and 10.0 mL·kg-1,indicating an effective middle dosage range,which was converted into clinical dosage about 37.1 to 112 mL each day.The research provided an experimental basis for clinical medication.
      作者: 姜丽 [1] 余兰彬 [2] 姚蓉 [2] 叶争荣 [2] 严小军 [1] 徐国良 [1]
      Author: Jiang Li [1] Yu Lanbin [2] Yao Rong [2] Ye Zhengrong [2] Yan Xiaojun [1] Xu Guoliang [1]
      作者单位: 江西中医药大学中医基础理论分化发展研究中心 南昌 330004;江西省中医病因生物学重点实验室 南昌 330004 江西中医药大学中医基础理论分化发展研究中心 南昌 330004
      年,卷(期): 2017, 19(1)
      分类号: R285
      在线出版日期: 2017年5月19日
      基金项目: 国家自然科学基金委地区项目(81360663):基于疾病过程对证治疗的中工复方药物代谢动力学研究,负责人:徐国良,江西省科技厅自然科学基金项目,基于代谢组分辨效应成分的中药复方药代动力学研究,负责人:姜丽,江西省卫生厅中医药科研项目(2015A039):基于微循环角度研究参附注射液对早、中期心源性休克大鼠的影响,负责人:姜丽