Improvement and Application of Acute Blood Stasis Rat Model Aligned with the 3Rs (Reduction, Refinement and Replacement) of Humane Animal Experimentation  

作　　者：HUANG Shuai XU Feng WANG Yin-ye SHANG Ming-ying WANG Chao-qun WANG Xuan CAI Shao-qing 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing(100191),China [2]Hubei Engineering Research Center of Viral Vector,Wuhan University of Bioengineering,Wuhan(430415),China [3]Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Peking University,Beijing(100191),China [4]Division of Pharmaceutical Analysis,School of Pharmaceutical Sciences,Peking University,Beijing(100191),China

出　　处：《Chinese Journal of Integrative Medicine》2020年第4期292-298,共7页中国结合医学杂志（英文版）

基　　金：Supported by the National Scie nee and Tech no logy Major Project for Major New Drugs Innovation and Development of China(No.2009ZX09502-023-4);National Technology Support Program(No.2006BAI09B06)。

摘　　要：Objective:To establish a novel cardiocentesis method for withdrawing venous blood from the right atrium,and to improve an acute blood stasis rat model using an ice bath and epinephrine hydrochloride(Epi)while considering the 3Rs(reduction,refinement,and replacement)of humane animal experimentation.Methods:An acute blood stasis model was established in male Sprague-Dawley rats by subcutaneous injection(s.c.)Epi(1.2mg/kg)administration at 0h,followed by a 5-min exposure to an ice-bath at 2h and s.c.Epi administration at 4h.Control rats received physiological saline.Rats were fasted overnight and treated with Angelicae Sinensis Lateralis Radix(ASLR)and Pheretima the following day.Venous blood was collected using our novel cardiocentesis method and used to test whole blood viscosity(WBV),prothrombin time(PT),activated partial thromboplastin time(APTT),and fibrinogen(FIB)8ntent.Results:The rats survived the novel cardiocentesis technique;WBV value returned to normal while hematological parameters such as hemoglobin level and red blood cell count were restored to>94%of the corresponding values in normal rats following a 14-day recovery.Epi(1.2 mg/kg,s.c.)combined with a 5-min exposure to the ice bath replicated the acute blood stasis rat model and was associated with the highest WBV value.In rats showing acute blood stasis,ASLR treatment[4g/(kg-d)for 8 days]decreased WBV by 9.98%,11.09%,9.34%,9.00%,7.66%,and 7.03%(P<0.05),while Pheretima treatment[2.6g/(kg?d),for 8 days]decreased WBV by 25.49%,25.94%,16.28%,17.76%,11.07%,and 7.89%(P<0.01)at shear rates of 1,3,10,30,100,and 180 s'1,respectively.Furthermore,Pheretima treatment increased APTT significantly(P<0.01).Conclusions:We presented a stable,reproducible,and improved acute blood stasis rat model,which could be applied to screen drugs for promoting blood circulation and eliminating blood stasis.

关 键 词：acute BLOOD STASIS rat model cardiocentesis whole BLOOD viscosity COAGULATION parameters Angelicae SINENSIS Lateralis RADIX PHERETIMA Chinese medicine syndrome 

分 类 号：R-332[医药卫生]