TGF-β1抑制Aβ_(1-42)诱导的海马神经炎症和神经元凋亡  

TGF-β1 protection against Aβ_(1-42)-induced neuroinflammation and neuronal apoptosis in rat hippocampus

作　　者：方小霞[1] 陈肖[2] 孙高林 邱一华 彭聿平 

机构地区：[1]南通大学医学院机能学实验室,南通226001 [2]南通大学医学院生理学系,南通226001

出　　处：《南通大学学报（医学版）》2015年第5期343-347,340,共6页Journal of Nantong University(Medical sciences)

基　　金：国家自然科学基金资助项目(81271323);江苏省研究生科技创新计划项目(KY22-0355);南通大学自然科学基金资助项目(12Z003)

摘　　要：目的 :研究转化生长因子-β1(transforming growth factor-β1,TGF-β1)在海马神经元与小胶质细胞共培养以及海马神经元单独培养两种体系抑制β淀粉样肽1-42(β-amyloid peptide1-42,Aβ1-42)诱导的海马炎症和神经元凋亡的神经保护作用。方法:采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)检测细胞活性;Western Blot法检测炎症因子环氧合酶-2(cyclooxygenase-2,COX-2)、诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达;激光共聚焦显微镜检测Neu N+/caspase-3+双阳性细胞数。结果 :在海马神经元与小胶质细胞的共培养体系中,Aβ1-42显著降低神经元活性,上调炎性介质COX-2、i NOS和TNF-α的蛋白表达,诱导了神经元凋亡,TGF-β1预处理能抑制Aβ1-42诱导的炎症介质COX-2、i NOS的蛋白表达上调,降低神经元凋亡;在海马神经元单独培养体系中,Aβ1-42降低了神经元活性,TGF-β1预处理抑制了炎症介质TNF-α的表达上调并抑制神经元凋亡。结论:TGF-β1在海马神经元与小胶质细胞共培养以及海马神经元单独培养两种体系中均能抑制Aβ1-42诱导的海马炎症和神经元凋亡。Objective:To explore the protective effects of transforming growth factor-β1(TGF-β1) onβ-amyloid peptide 1-42 (Aβ1-42)-induced neuroinflammation and neuronal apoptosis in both the hippocampal neuron-microglia co-cultures and hippocampal neurons cultures. Methods:Methyl thiazdyl tetrazolium(MTT) assay was used to detect cell viability, Western Blot analyses were employed to examine the expression of tumor necrosis factor-α(TNF-α), cyclooxygenase(COX)-2, inducible nitric oxide synthase(iNOS). Immunofluorescence staining was used to detect the number of NeuN+/caspase-3+double-labeled neurons. Results: In the hippocampal neuron-microglia co-cultures, Aβ1-42 up-regulated the expression of inflammatory mediators, including COX-2, iNOS, and TNF-α, increased the neurons apoptosis, TGF-β1 pretreatment ameliorated the pro-inflammatory effects caused by Aβ1-42. In hippocampal neurons cultures, TGF-β1 pretreatment inhibited Aβ1-42-induced up-regulation of expression of TNF-α, but did not inhibit Aβ1-42-induced up-regulation of expression of COX-2, decrease the neurons apoptosis . Conclusions: TGF-β1 has a significant neuroprotective effect by inhibiting the Aβ1-42-induced neuroinflammation and neuronal apoptosis in rat hippocampus in both the hippocampal neuron-microglia co-cultures and hippocampal neurons cultures.

关 键 词：海马神经元 小胶质细胞 神经炎症 凋亡 转化生长因子-Β1 β淀粉样肽1-42 

分 类 号：R285[医药卫生—中药学]