摘要
目的:探讨AMPK激动剂AICAR对糖氧剥夺(oxygen-glucose deprivation,OGD)损伤后原代星形胶质细胞炎性反应的影响及对损伤神经元的保护作用。方法:通过构建原代培养星形胶质细胞和神经元的OGD模型,在正常培养的原代星形胶质细胞中加入对照溶剂和AICAR(0.5 mmol/L),后给予OGD处理,在复氧第12小时通过ELISA检测促炎因子肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6和IL-1β的表达变化,通过Western blotting方法检测磷酸化p38的蛋白表达;再将上述对照组和AICAR组OGD处理后的星形胶质细胞培养液,加入OGD损伤后的原代培养神经元中,通过LDH检测及免疫荧光双标方法,检测AICAR对缺糖缺氧损伤神经元的保护作用。结果:在原代培养神经元及星形胶质细胞OGD损伤模型中,与对照组比较,AICAR组显著地降低了OGD损伤后星形胶质细胞分泌的促炎因子TNF-α、IL-6和IL-1β(P<0.01),抑制p38磷酸化,且明显降低了缺糖缺氧造成的神经元损伤(P<0.01),促进损伤的神经突起修复。结论:AICAR抑制OGD损伤后星形胶质细胞炎性因子的释放,对OGD损伤神经元具有保护作用。
Objective： To evaluate the effects of the AMPK activator AICAR on the inflammatory response of astrocytes and protecting the neurons after oxygen-glucose deprivation OGD-treatment. Methods： The OGD-treated model in primary cultured neurons and astrocytes was established. AICAR（ 0. 5 mmol/L） and control solution were added into the primary cultured astrocytes,then which was treated with OGD. After 12 h of reoxygenation,the expression levels of pro-inflammatory cytokines（ TNF-α,IL-6 and IL-1β） were analyzed using ELISA,and the level of phosphorylated p38 was analyzed using Western blot. The astrocytic medium of control group and AICAR group treated with OGD were added into the primary cultured neurons injured by OGD. The neuroprotective effect of AICAR on the OGD-injured neurons was analyzed by LDH and immunofluoresent double staining. Results： In the OGD-treated primary cultured neurons and astrocytes,AICAR significantly reduced the levels of TNF-α,IL-6 and IL-1β secreted from OGD-treated astrocytes,inhibited the phosphorylation of p38,reduced the OGD-induced injury of neurons,and promoted the recovery of neurites compared with control group. Conclusions： AICAR can inhibit the secretion of inflammatory cytokines from OGD-treated astrocytes,and protect the OGD-treated neurons.
作者
赵晶晶
杨振坤
孙洁
王伟
董文艳
陈静瑜
ZHAO Jing-jing;YANG Zhen-kun;SUN Jie;WANG Wei;DONG Wen-yan;CHEN Jing-yu(Center of Clinical Research;Division of Cardiothoracic Surgery;Department of Anesthesiology,The Affiliated Wuxi People′s Hospital of Nanjing Medical University,Wuxi Jiangsu 214023,China)
出处
《蚌埠医学院学报》
CAS
2018年第4期450-453,共4页
Journal of Bengbu Medical College
基金
国家自然科学基金项目(30971464)
南京医科大学科技发展基金重点项目(2017NJMUZD125)
江苏省无锡市卫生计生委科研项目(Q201715)
