TGF-β1对Aβ1-42诱导海马神经元-小胶质细胞共培养体系中细胞因子表达和分泌的影响

目的：探讨在海马神经元和小胶质细胞共培养体系中转化生长因子-β1（TGF-β1）对β淀粉样肽1-42（Aβ_1-42）诱导的小胶质细胞激活表达和分泌细胞因子的影响。方法：将大鼠海马神经元和小胶质细胞进行共同培养，于共同培养后第5日，加入TGF-β1（5 or 20 ng/ml），1 h后加入Aβ_1-42（5 μmol/L），继续培养72 h后用于后续实验，Western blot法检测诱导型一氧化氮合酶（iNOS）的蛋白表达；Real-time PCR和ELISA法检测肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）和胰岛素样生长因子（IGF-1）的mRNA表达和分泌。结果：在共同培养的海马神经元与小胶质细胞体系中，Aβ_1-42诱导炎症因子iNOS、TNF-α和IL-1β的表达和/或分泌上调，神经营养因子IGF-1表达下调，TGF-β1预处理削弱上述Aβ_1-42的作用。结论：TGF-β1明显抑制Aβ_1-42诱导的小胶质细胞激活引起的炎性细胞因子的增加和神经营养因子的减少。

Effects of TGF-β1 on the expression and secretion of cytokines induced by Aβ1-42 in hippocampal neuron and microglia co-cultures

Objective: To investigate the neuroprotective effects of transforming growth factor beta 1(TGF-β1) on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neurons and microglial co-cultures. Methods: Hippocampal neurons and microglia obtained from SD rat were co-cultured. TGF-β1 was applied on day 5 after the neurons and microglia co-cultures were incubated at the concentrations of 5 or 20 ng/ml, Aβ_1-42 was added 1 h following TGF-β1 application at a concentration of 5 μmol/L. They were incubated for 72 h and then assessed for further studies. Western blot analyses were employed to examine the expression of inducible nitric oxide synthase (iNOS); Real-time PCR and ELISA were used to detect the mRNA expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and insulin-like growth factor-1 (IGF-1). Results: In the hippocampal neuron-microglia co-cultures, Aβ_1-42 induced upregulation of iNOS, TNF-α and IL-1β, downregulation of IGF-1. TGF-β1 pretreatment ameliorated the pro-inflammatory effects caused by Aβ_1-42. Conclusion: TGF-β1 significantly inhibits the increase in inflammatory cytokines and the decrease in neurotrophic factor which are caused by Aβ_1-42-induced microglia activation.