Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Neurochem Res. 2018 Aug;43(8):1599-1607. doi: 10.1007/s11064-018-2574-z. Epub 2018 Jun 13.
Complement component C3 (C3), a key factor in the complement system, is heavily involved in various inflammation-associated diseases. However, it remains obscure for its role in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury in diabetes. A transient middle cerebral artery occlusion (tMCAO) model was used for cerebral I/R injury in streptozotocin-induced diabetic mice. Cerebral infarct volume and neurological function were measured at different times of reperfusion. Complement C3 was measured by ELISA and western blotting. It was observed that complement C3 expression was increased in cerebral I/R injury of diabetic mice, whereas complement C3 deficiency abrogated the activation and injury. Furthermore, activating complement C3 promotes TLR2/NFκB activation after I/R injury in diabetic mice, which is inhibited by of the silencing of TLR2. Taken together, our data demonstrate that complement C3 promotes cerebral I/R injury via the TLR2/NFκB pathway in diabetic mice, and regulating the complement C3/TLR2/NFκB pathway may be a novel target for therapeutic intervention in diabetic stroke.
补体成分 C3（C3）是补体系统中的关键因子，广泛参与各种与炎症相关的疾病。然而，其在糖尿病性脑缺血/再灌注（I/R）损伤发病机制中的作用仍不清楚。本研究使用链脲佐菌素诱导的糖尿病小鼠短暂性大脑中动脉闭塞（tMCAO）模型来研究脑 I/R 损伤。在不同的再灌注时间点测量脑梗死体积和神经功能。通过 ELISA 和 Western blot 测定补体 C3。结果观察到，糖尿病小鼠脑 I/R 损伤时补体 C3 表达增加，而补体 C3 缺乏则可阻断其激活和损伤。此外，激活补体 C3 可促进糖尿病小鼠 I/R 损伤后 TLR2/NFκB 的激活，而 TLR2 的沉默可抑制该作用。综上所述，本研究数据表明，补体 C3 通过 TLR2/NFκB 通路促进糖尿病小鼠脑 I/R 损伤，调节补体 C3/TLR2/NFκB 通路可能是糖尿病性中风治疗干预的新靶点。
