Gill Ramanjit, Kemp John A, Sabin Caroline, Pepys Mark B
F Hoffman-La Roche Ltd, Preclinical CNS Research, Pharmaceuticals Division, Basel, Switzerland.
J Cereb Blood Flow Metab. 2004 Nov;24(11):1214-8. doi: 10.1097/01.WCB.0000136517.61642.99.
Human C-reactive protein (CRP), the classic acute phase plasma protein, increases in concentration after myocardial infarction and stroke. Human CRP binds to ligands exposed in damaged tissue and can then activate complement and its proinflammatory functions. In contrast, rat CRP, which binds to similar ligands, does not activate complement. In the present study, systemic complement depletion with cobra venom factor in adult rats subjected to middle cerebral artery occlusion did not affect cerebral infarct size, indicating that circulating complement does not contribute to injury in this model. However, we have previously reported that administration of human CRP to rats undergoing coronary artery ligation caused a marked increase in size of the resulting myocardial infarction, associated with codeposition of human CRP and rat complement in the infarcts. In the present study, we show that adult rats subjected to middle cerebral artery occlusion and then treated with human CRP similarly developed significantly larger cerebral infarcts compared with control subjects receiving human serum albumin. Human CRP can thus contribute to ischemic tissue damage in the brain as well as in the heart, and inhibition of CRP binding may therefore be a promising target for tissue protective acute therapeutic intervention in stroke as well as in myocardial infarction.
人类C反应蛋白（CRP）是经典的急性期血浆蛋白，在心肌梗死和中风后浓度会升高。人类CRP与受损组织中暴露的配体结合，进而激活补体及其促炎功能。相比之下，大鼠CRP虽然能与相似配体结合，但不会激活补体。在本研究中，对成年大鼠进行大脑中动脉闭塞手术，并使用眼镜蛇毒因子进行全身补体耗竭处理，结果并未影响脑梗死面积，这表明在该模型中循环补体对损伤并无作用。然而，我们之前报道过，给接受冠状动脉结扎的大鼠注射人类CRP会导致随后心肌梗死面积显著增大，梗死区域同时出现人类CRP和大鼠补体的共沉积。在本研究中，我们发现，与接受人血清白蛋白的对照组相比，成年大鼠大脑中动脉闭塞后再接受人类CRP治疗，同样会出现明显更大的脑梗死。因此，人类CRP可能会导致大脑以及心脏的缺血性组织损伤，抑制CRP结合可能是中风和心肌梗死组织保护性急性治疗干预的一个有前景的靶点。
