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目的:通过制备铅中毒模型诱导原代培养神经元凋亡来探讨neuregulin1(NRG1)的抗神经元凋亡作用及机制。方法:将NRG1和(或)PI3K抑制剂Wortmannin(10μmol·L-1)加入到原代培养神经元的培养基中进行预孵育4 h,然后用醋酸铅刺激原代神经元4 h,观察NRG1的抗凋亡作用及机制。用Caspase3活力变化来检测神经元内凋亡的表达水平,同时,Western blot检测NRG1β1和p-Akt的水平。结果:在用铅刺激原代神经元后,细胞凋亡明显,表现为Caspase-3活力显著增加(P<0.05)。NRG1能抑制铅染毒引起的Caspase-3活力增加(P<0.05)。NRG1可上调p-Akt的表达,应用PI3K/Akt的抑制剂Wortmannin后,Wortmannin能拮抗NRG1的升高p-Akt及抗凋亡作用(P<0.05)。结论:NRG1显著抵抗铅诱导的神经元凋亡,PI3K/Akt途径参与介导NRG1的抗神经元凋亡作用。
OBJECTIVE: To investigate the neuroprotective effect of neuregulin1 (NRG1) on neuronal apoptosis induced by lead poisoning model and its mechanism. Methods: NRG1 and / or PI3K inhibitor Wortmannin (10μmol·L-1) were added to the primary cultured neurons for 4 hours. Primary neurons were stimulated with lead acetate for 4 hours to observe the effects of NRG1 Anti-apoptotic effects and mechanisms. Caspase3 vitality changes were used to detect neuronal apoptosis expression levels, while Western blot detection of NRG1β1 and p-Akt levels. Results: After the primary neurons were stimulated by lead, the apoptosis of the primary neurons was obvious and the activity of Caspase-3 was significantly increased (P <0.05). NRG1 inhibited the increase of Caspase-3 activity induced by lead exposure (P <0.05). NRG1 up-regulated the expression of p-Akt. Wortmannin could antagonize the up-regulation of p-Akt and anti-apoptotic effect of NRG1 (P <0.05) after PI3K / Akt inhibitor Wortmannin. CONCLUSION: NRG1 is significantly resistant to lead-induced neuronal apoptosis. The PI3K / Akt pathway is involved in the anti-neuronal apoptosis of NRG1.