在多创伤后抑制纤维素素的上调调节可以减轻小鼠的血栓形成
Monica S Seadler1, Francesca Ferraresso, Muskan Bansal
1From the Department of Surgery (M.S.S., M.B., A.H., W.G.H., M.d.M., C.J.K.), Division of Trauma, Medical College of Wisconsin; Versiti Blood Research Institute (M.S.S., F.F., M.B., A.H., W.G.H., M.R.D., C.J.K.), Milwaukee, Wisconsin; Michael Smith Laboratories (F.F., C.J.K.), and Department of Biochemistry and Molecular Biology (F.F., C.J.K.), University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine (M.J.F.), and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (M.J.F.); UNC Blood Research Center (M.J.F.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Surgery (M.R.D.), Division of Vascular Surgery, and Departments of Biochemistry (C.J.K.), Biomedical Engineering (C.J.K.), and Pharmacology and Toxicology (C.J.K.), Medical College of Wisconsin, Milwaukee, Wisconsin.
通过小干扰性核糖核酸 (siRNA) 对纤维素素 (siFibrinogen) 预防多创伤后纤维素素增加,显著减少了血栓形成. 这种新的方法显示出预防创伤患者静脉血栓栓塞 (VTE) 的前景.
科学领域:
- 生物医学研究的研究.
- 分子生物学分子生物学
- 创伤医学是一种创伤医学.
背景情况:
- 多创伤会引发全身炎症和纤维素素水平升高,增加血栓形成风险和二次器官损伤.
- 目前的治疗方法缺乏预防创伤后纤维素生成性高血症的药物.
- 假设:在多创伤后抑制纤维素素增加可以抑制血栓形成.
研究的目的:
- 研究用siRNA准纤维素素以预防多创伤后血栓形成的疗效.
- 在小鼠模型中评估siFibrinogen对高纤维素生成症和血栓形成的影响.
主要方法:
- 脂质纳米颗粒封装的siRNA对纤维素原 (siFibrinogen) 的开发.
- 在小鼠中诱导多创伤,然后给予不同的siFibrinogen剂量或控制siRNA.
- 通过下静脉绑和血栓重量分析测量纤维素素水平和评估静脉血栓栓塞 (VTE).
主要成果:
- siFibrinogen有效地预防了多重创伤后的高纤维素生成症,而不会导致急性低纤维素生成症.
- 从受伤后6小时到7天观察到纤维素水平的显著降低.
- 与0/9对照组相比,siFibrinogen治疗显著降低了血栓重量,并完全保护了12/18只小鼠免受血栓形成.
结论:
- 对纤维素因子的siRNA的施用减轻了纤维素因子的增加和多创伤后的血栓形成.
- siFibrinogen为创伤患者的VTE预防提供了一个有前途的新疗法策略.
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