Complement Component C3 Promotes Cerebral Ischemia/Reperfusion Injury Mediated by TLR2/NFκB Activation in Diabetic Mice
Complement Component C3 Promotes Cerebral Ischemia/Reperfusion Injury Mediated by TLR2/NFκB Activation in Diabetic Mice
复制标题
补体成分 C3 促进糖尿病小鼠 TLR2/NFkappaB 激活介导的脑缺血/再灌注损伤。
DOI：
10.1007/s11064-018-2574-z
复制
发表时间：
2018-08-01
影响因子：
4.4
通讯作者：
Dai, Haibin
中科院分区：
文献类型：
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作者：
Lin, Zheng;Lin, Haoran;Dai, Haibin
补体成分C3（C3）是补体系统中的一个关键因子，与多种炎症相关疾病密切相关。然而，它在糖尿病脑缺血/再灌注损伤的发病机制中的作用仍不清楚。采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）模型观察脑I/R损伤。在再灌注的不同时间测量脑梗死体积和神经功能。补体C3用ELISA和Western印迹法测定。观察到糖尿病小鼠脑I/R损伤中补体C3表达增加，而补体C3缺乏则消除了活化和损伤。此外，激活补体C3促进糖尿病小鼠I/R损伤后TLR 2/NF κ B激活，这被TLR 2沉默所抑制。综上所述，我们的数据表明，补体C3通过TLR 2/NF κ B通路促进糖尿病小鼠脑I/R损伤，调节补体C3/TLR 2/NF κ B通路可能是糖尿病脑卒中治疗干预的新靶点。
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/NF kappa B 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/NF kappa B pathway in diabetic mice, and regulating the complement C3/TLR2/NF kappa B pathway may be a novel target for therapeutic intervention in diabetic stroke.