血瘀证与血栓形成病证结合动物模型的研究

目的:以细菌内毒素(LPS)与角叉菜胶(Ca)两种因素联合造模,制备一种方法简便、稳定的血瘀证和血栓形成病证结合动物模型。方法:将大鼠随机分成正常对照组,LPS/Ca造模组。造模组动物先每只给予Ca 5 mgip,16 h后给予LPS 50μg.kg^-1iv,以注射LPS时作为试验的0 h。于造模后24 h观察血栓形成,于造模后不同的时间点分批观察微循环变化、血液流变学指标、凝血指标和炎症反应指标。结果:LPS/Ca联合造模可建立稳定、重复性良好的血栓形成模型,不需剖杀动物在尾部即可肉眼观察和定量测量血栓。该模型还表现出微循环障碍以及全血黏度增高、血小板聚集率异常等血液流变学指标的改变,同时还由于血栓形成消耗了大量凝血因子和血小板,而表现出凝血指标延长。结果表明该模型具有明显的血瘀证客观指标的改变。模型早期动物血液中的炎性因子TNFα和IL-6明显增高,故该模型符合炎症诱导的热毒血瘀证特点。结论:LPS/Ca联合造模可建立一种操作简便、稳定的热毒血瘀证与血栓形成病证结合动物模型。

Development of an animal model of blood stasis syndrome and thrombosis

OBJECTIVE: To develop an animal model of thrombosis and blood stasis syndrome in rats by using lipopolysaccharide (LPS) in combination with carrageenan (Ca). METHOD: SD rats in control group were randomly divided into control group and model group (LPS/Ca treatment). The rats in model group were firstly treated with Ca ip, and followed by LPS iv sixteen hours later. The rats in control group were given normal saline (NS). The moment of LPS iv was served as 0 h for the observation. The ear microcirculation, blood rheology parameters (whole blood viscosity etab, plasma viscosity etap and platelet aggregation PA), cruor parameters (thrombin time TT, prothrombin time PT, and partial thromboplastin time APIT) and inflammation factors (TNFalpha, IL-6) were observed at different time after treatment. RESULT: LPS/Ca combinatory treatment can induce a stable and repeatable thrombosis animal model. The thrombus can be observed on the tails of rats by naked eyes, and can be quantitatively measured without necessary of autopsy. Obstacle in microcirculation, increase in whole blood viscosity (etab) and a change of platelets aggregation (PA) rate were observed after LPS/Ca treatment. Cruor parameters were significantly prolonged due to large consumption of cruor factors and platelets. The concentration of inflammation factors TNFalpha and IL-6 in blood was obviously increased at the early stage of the model. The results indicate that this animal model has the characteristics of blood stasis syndrome caused by pyrogen and toxin accompanied by thrombosis. CONCLUSION: LPS/Ca combinatory treatment can induce a easily practicable and repeatable animal model characterized as thrombosis and blood stasis syndrome