抑制补充成分C3可以减少阿波利波蛋白E3-Leiden转基因小鼠的静脉移植动脉样硬化
A Schepers1, M R de Vries, C J van Leuven
1Gaubius Laboratory, TNO Quality of Life, Leiden, The Netherlands.
Circulation
|December 6, 2006
概括
补体级联有助于静脉移植加厚和动脉样硬化,建议它作为预防移植失败的治疗点. 在小鼠模型中,抑制补充成分C3减少了炎症和移植物加厚.
科学领域:
- 免疫学 免疫学 免疫学
- 血管生物学 血管生物学
- 手术研究的研究.
背景情况:
- 静脉移植失败通常是由内脏增生和加速动脉样硬化引起的.
- 炎症是这些病理过程的关键驱动因素.
- 补体系统在静脉移植动脉样硬化中的作用在很大程度上仍未被探索.
研究的目的:
- 调查补体级联在静脉移植动脉样硬化的发展中的参与.
- 确定向补充剂是否可以成为静脉移植失败的治疗策略.
主要方法:
- 使用了一种小鼠模型,在常见的动脉中进行静脉插曲.
- 进行了免疫组织化学和定量mRNA分析,以检测补充成分 (C1q,C3,C9) 和调节蛋白 (CD59,补充受体相关基因).
- 使用配方受体相关基因y-Ig干扰C3激活和用蛇毒因子抑制C3被用于评估治疗效果.
主要成果:
- 在4周内观察到静脉移植的加厚和补体成分 (C1q,C3,C9) 的沉积.
- 在加厚的移植中检测到C1q,C3,CD59和补充受体相关基因的局部mRNA表达.
- 抑制C3激活显著降低了静脉移植加厚,C3 / C9沉积和炎症细胞透,同时也影响了细胞亡和增殖.
结论:
- 补体级联在静脉移植加厚方面发挥着重要作用.
- 向补充激活,特别是C3,显示出作为预防静脉移植失败的治疗方法的潜力.
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