抑制曼诺结合性莱克可以减少血后心肌再注射损伤
J E Jordan1, M C Montalto, G L Stahl
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circulation
|September 19, 2001
概括
莱克补充通路在心脏病发作期间被激活,导致组织损伤. 通过抗体抑制这种途径,通过减少炎症和免疫细胞透来保护心脏.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管生物学 心血管生物学
- 补充系统 补充系统
背景情况:
- 补体系统对于先天性和适应性免疫是至关重要的,具有三个激活途径:古典,替代和莱克.
- 虽然补体系统在缺血-再输液损伤中的作用是已知的,但莱克通路的具体参与仍然不清楚.
研究的目的:
- 调查莱克补充通路在心肌缺血-再输液损伤中的作用.
- 在心脏病发作的小鼠模型中评估阻断莱克通路的治疗潜力.
主要方法:
- 单克隆抗体 (mAbs) 针对老鼠的曼诺结合性学菌素 (rMBL) 产生.
- 在试验室和体内,使用心肌缺血-再输血 (冠状动脉封闭后再输血) 的老鼠模型评估了mAbs的抑制能力.
- 测量包括补充C3沉积,肌酸激酶损失,心脏病发作大小,中性粒细胞透和促炎基因的表达.
主要成果:
- 一个mAb (P7E4) 在体外和体内有效抑制了莱克通路.
- P7E4治疗显著降低了补充C3沉积,心肌损伤 (肌激酶损失,心脏病发作大小) 和中性粒细胞在心脏中的透.
- 此外,P7E4还减弱了关键的促炎基因的表达,包括细胞间粘附分子-1,血管细胞粘附分子-1和互白素-6.
结论:
- 莱克补充通路在心肌缺血-再输动过程中被激活,并导致组织损伤.
- 通过抑制mAbs阻断莱克通路,通过减轻中性粒细胞透和减少促炎反应来提供心脏保护.
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