氯化铁结合凝血酶构建兔静脉窦血栓模型

Establishment of cerebral venous sinus thrombosis model in rabbits by using ferric chloride combined with thrombin injection

目的探讨上矢状窦(SSS)局部贴敷氯化铁并注入凝血酶诱导颅内静脉窦血栓形成(CVST)动物模型构建方法,评估其可行性及应用价值。方法 39只新西兰大白兔随机分成A、B、C组,每组13只。A组兔SSS局部贴敷0.9%氯化钠溶液棉片10 min,B组局部贴敷40%氯化铁棉片10 min,C组局部贴敷40%氯化铁棉片5 min并注入凝血酶。建模术后即刻作全脑血管DSA,判断有无血栓形成,术后2 d每组随机抽取3只兔作2,3,5-氯化三苯基四氮唑(TTC)染色,其余10只于术后7 d复查DSA,计算血栓再通率,并作组织病理学检查。结果 B组、C组均可诱导SSS血栓形成及其周围脑梗死、水肿及炎性细胞聚集等病理改变。与B组相比,C组建模术后7 d血栓再通率明显降低(10%对70%),且伴有周围皮层静脉血栓形成及皮层下淤点性出血。结论兔SSS局部贴敷氯化铁并注入凝血酶诱导CVST模型的方法有效可行,形成血栓更加稳定,其发生机制及病理生理与临床相似,可用于CVST基础和临床试验研究。

Objective To discuss the establishment of cerebral venous sinus thrombosis（CVST）model in rabbits by local application of ferric chloride at sinuses sagittalis superior（SSS） combined with thrombin injection, and to evaluate its feasibility and application value. Methods A total of 39 New Zealand white rabbits were randomly and equally divided into three groups with 13 rabbits in each group. local application of cotton piece saturated with saline at SSS for 10 minutes was performed for the rabbits of group A, SSS local application of cotton piece saturated with 40% ferric chloride for 10 minutes was adopted for the rabbits of group B, while SSS local application of cotton piece saturated with 40% ferric chloride for 5 minutes together with injection of thrombin was carried out for the rabbits of group C. Whole cerebral DSA was performed immediately after modeling to judge if there was formation of thrombosis. Two days after the modeling, every 3 rabbits from each group were sacrificed to make 2, 3, 5-chloride triphenyl tetrazole（TTC） staining. Seven days after the modeling, the remaining 10 rabbits of each group were examined with DSA, the vascular recanalization rates were calculated, and the histopathological examination was made.Results In group B and group C, SSS thrombosis with surrounding cerebral infarction, edema, inflammatory cell aggregation and other pathological changes were observed. The 7-day vascular recanalization rate in group C was strikingly lower than that in group B（10% vs 70%, P0.05）. Surrounding cortical vein thrombus and subcortex petechial hemorrhages were obviously seen in group C. Conclusion For the establishment of CVST model in rabbits, local application of ferric chloride at SSS together with thrombin injection is effective and feasible. The thrombus thus induced is quite stable, and its pathogenesis and pathophysiology are quite similar to clinical manifestations. Therefore, this method can be used for basic research and clinical trials of CVST.