TAK-242 对Aβ25-35 诱导大鼠海马神经元损伤的作用及其机制研究

Effect of TAK-242 on β-amyloid peptide-induced neurotoxicity in hippocampi of rats and its mechanism

摘要:

目的 探讨TAK-242 对β- 淀粉样蛋白25-35（Aβ25-35）诱导的大鼠海马神经元损伤的作用及其相关机制。方法 用Aβ25-35 注射大鼠双侧海马复制阿尔兹海默病的动物模型，TAK-242 腹腔注射进行治疗，Nissl 染色观察大鼠海马CA3 区神经元的形态和数量，Western blot 检测大鼠海马Toll 样受体4（TLR4）和髓样分化因子88（MyD88）蛋白的表达，酶联免疫吸附法检测大鼠海马白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）表达水平。结果 大鼠海马注射Aβ25-35 后引起大鼠海马CA3 区神经元破坏和数量减少，而TAK-242 可以抵抗Aβ25-35 所造成的神经毒性并保护海马神经元，同时TAK-242 可降低Aβ25-35 所引起的海马组织内TLR4、MyD88、IL-1β 和TNF-α 表达升高。结论 TAK-242 可以通过抑制TLR4/MyD88信号通路，降低炎症因子IL-1β 和TNF-α 水平，从而保护大鼠海马神经元抵抗Aβ25-35 诱导的神经毒性。

Abstract:

Abstract: Objective To explore the effect of TAK-242 on β-amyloid peptide25-35 (Aβ25-35)-induced neural injury in rat hippocampi and the potential mechanism. Methods Aβ25-35 was injected into bilateral hippocampi of rats to build up Alzheimer's disease (AD) mode, then TAK-242 was injected to rat intraperitoneally. The morphological features and the amount of neurons in the CA3 area of hippocampi were observed after Nissl staining. The expressions of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) proteins were detected by Western blot. The levels of IL-1β and TNF-α were tested by ELISA. Results Injection of Aβ25-35 into hippocampi caused neuronal damage and loss in the CA3 area, however, TAK-242 could protect neurons in hippocampi against Aβ25-35-induced injury. Meanwhile, TAK-242 could reduce Aβ25-35-induced increase of TLR4, MyD88, IL-1β and TNF-α proteins. Conclusions TAK-242 could inhibit Aβ25-35-induced toxic role on neurons in the CA3 area of hippocampi through down-regulation of the TLR4/MyD88 signaling pathway and reduction of inflammatory factors IL-1β and TNF-α.