目的:构建稳定的大鼠门静脉血栓形成(PVT)模型,并在此基础上探讨尿激酶溶栓治疗的时间窗。
方法:结合无水乙醇破坏门静脉内皮和血流淤滞构建大鼠PVT模型。将48只PVT造模后的大鼠分为对照组和实验组,每组24只大鼠。实验组和对照组给予尿激酶治疗和生理盐水尾静脉注射,分别。观察并比较两组大鼠造模后1、3、5天PVT形成情况,分别。
结果:成功构建了稳定的大鼠PVT模型。PVT长度无显著差异,门静脉湿重,造模成功后第1、3和5天,对照组大鼠管腔阻塞面积百分比(P>0.05)。造模后1天与对照组大鼠比较,无组织血栓管腔面积的百分比显着降低(P<0.0001),在建模后3天和5天,对照组大鼠的PVTs中,有组织的血栓腔面积百分比显着增加(P<0.0001)。尿激酶溶栓治疗后,实验组大鼠血浆纤维蛋白原(FBG)水平较对照组明显降低(P<0.0001),实验组大鼠血浆D-二聚体(D2D)水平明显高于对照组(P<0.0001)。此外,与对照组相比,实验组在建模后1、3和5天的凝血酶原时间(PT)延长(P=0.0001)。与对照组相比,造模后第1天实验组大鼠门静脉湿重和PVT长度显著降低(P<0.05),而两组大鼠在造模后3天和5天没有发现这些差异(P>0.05)。造模后第1、3、5天,实验组无组织血栓面积百分比较对照组明显降低(P<0.05),而组织化血栓的管腔面积百分比在两组之间没有显着差异(P>0.05)。
结论:无水乙醇破坏门静脉内皮结合血瘀法制备大鼠PVT模型的方法是可行和可重复的。此外,尿激酶治疗大鼠PVT的最佳溶栓时间窗是血栓形成的早期,当纤维蛋白含量最高。
OBJECTIVE: To construct a stable rat portal vein thrombosis (PVT) model and explore the time window of urokinase thrombolytic therapy on this basis.
METHODS: Constructing a rat PVT model by combining anhydrous ethanol disruption of portal endothelium with stasis of blood flow. Forty-eight rats after PVT modeling were divided into control group and experimental group, with 24 rats in each group. The experimental and control groups were given urokinase treatment and saline tail vein injection, respectively. The two groups of rats were observed and compared for PVT formation at 1, 3 and 5 days after modeling, respectively.
RESULTS: A stable rat PVT model was successfully constructed. No significant differences were found in PVT length, portal vein wet weight, and percentage of luminal occlusion area in the control rats at 1, 3, and 5 days after successful modeling (P > 0.05). Compared with control rats 1 day after modeling, the percentage of non-organized thrombus luminal area was significantly decreased (P < 0.0001), and the percentage of organized thrombus luminal area was significantly increased (P < 0.0001) in the PVTs of control rats at 3 and 5 days after modeling. After thrombolytic treatment with urokinase, plasma
fibrinogen (FBG) levels were significantly decreased in the experimental group of rats compared with the control group (P < 0.0001), and plasma D-dimer (D2D) levels were significantly increased in the experimental group of rats compared with the control group (P < 0.0001). In addition, we observed prolongation of prothrombin time (PT) in the experimental group at 1, 3 and 5 days after modeling compared to the control group (P = 0.0001). Compared with the control group, portal vein wet weight and PVT length were significantly decreased in the experimental group of rats at 1 day after modeling (P < 0.05), whereas these differences were not found in the two groups of rats at 3 and 5 days after modeling (P > 0.05). The percentage of non-organized thrombus area in the experimental group was significantly decreased compared with that in the control group at 1, 3, and 5 days after modeling (P < 0.05), whereas there was no significant difference in the percentage of lumen area of organized thrombus between the two groups (P > 0.05).
CONCLUSIONS: The method of producing a rat PVT model by destroying the endothelium of the portal vein by anhydrous ethanol combined with blood flow stasis is feasible and reproducible. In addition, the optimal time window for thrombolysis in the treatment of PVT in rats using urokinase is the early stage of thrombosis, when the fibrin content is highest.