Gong Ping, Zhao Hong, Hua Rong, Zhang Mingyue, Tang Ziren, Mei Xue, Cui Juan, Li Chunsheng
Department of Emergency, First Hospital affiliated to Dalian Medical University, Dalian, China.
Department of Emergency, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
J Cereb Blood Flow Metab. 2015 Aug;35(8):1289-95. doi: 10.1038/jcbfm.2015.41. Epub 2015 Mar 11.
Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection.
补体激活与缺血/再灌注损伤有关。本研究旨在确定轻度低温（HT）是否能抑制心脏骤停复苏后全身和脑内补体的激活。16只从8分钟未经治疗的室颤中复苏的小型猪被随机分为两组：HT组（n = 8），接受12小时的HT治疗（33°C）；常温组（n = 8），除不进行降温外，其他治疗与HT组相似。在基线以及自主循环恢复（ROSC）后0.5、6、12和24小时采集血样。ROSC后24小时采集大脑皮质。使用酶联免疫吸附测定法检测补体和促炎标志物。ROSC后24小时评估神经功能缺损评分。常温下，ROSC后24小时内C1q、Bb、甘露糖结合凝集素（MBL）、C3b、C3a、C5a、白细胞介素-6和肿瘤坏死因子-α水平显著升高。然而，HT可显著降低这些升高水平。低温降低了ROSC后24小时脑内C1q、MBL、C3b和C5a的含量。低温处理的猪比常温处理的猪神经功能结局更好。总之，ROSC后补体通过经典、替代和MBL途径被激活。低温抑制全身和脑内补体激活，这可能为脑保护提供一种额外机制。
