Complement component C3 mediates inflammatory injury following focal cerebral ischemia
Complement component C3 mediates inflammatory injury following focal cerebral ischemia
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DOI：
10.1161/01.res.0000232544.90675.42
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发表时间：
2006-07-21
影响因子：
20.1
通讯作者：
Connolly, E. Sander, Jr.
中科院分区：
文献类型：
--
作者：
Mocco, J.;Mack, William J.;Connolly, E. Sander, Jr.
补体级联与脑缺血/再灌注损伤有关，最近的研究表明，补体抑制是治疗急性卒中的一种有前途的选择。然而，由于对哪些补体亚组分导致缺血后损伤的了解不足，临床上有用的治疗方法的发展受到了阻碍。为了解决这个问题，我们让缺乏特定补体蛋白(C1q，C3，C5)的小鼠遭受短暂性局灶性脑缺血。在研究的品系中，只有C3(-/-)小鼠受到保护，这表明梗塞体积(P<；0.01)和神经功能缺陷评分(P<；0.05)都减少了34%。C3缺乏的小鼠还表现出粒细胞渗透减少(P<；0.02)和氧化应激减少(P<；0.05)。最后，给予C3a受体拮抗剂导致相应的神经功能改善和每搏量减少(P<；0.05)。综上所述，这些结果证实C3激活是中风后补体相关炎症组织损伤的关键成分，并提示C3a过敏毒素介导的机制。
The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3(-/-) mice were protected, as demonstrated by 34% reductions in both infarct volume (P < 0.01) and neurological deficit score (P < 0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P < 0.02) and reduced oxidative stress (P < 0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P < 0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.