南方医科大学学报2018，Vol.38Issue(5)：567-571,5.
Caspase-1活化在胆红素诱导的大鼠海马神经元损伤中的作用
Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons
摘要
Abstract
Objective To investigate the role of caspase-1 activation in bilirubin-induced neuronal injury and the protective effect of VX-765 against bilirubin-induced neurotoxicity in cultured primary rat hippocampal neurons. Methods Cultured primary rat hippocampal neurons were exposed to DMSO(control group),50 μmol/L bilirubin,or 50 μmol/L bilirubin 1 h after 50 μmol/L VX-765 treatment.The expressions of NLRP3 and caspase-1 in the neurons were detected by Western blotting,and the relative cell survival and death rates were assessed with a modified MTT assay, lactate dehydrogenase assay and Typan blue staining. Interleukin-18 (IL-18) concentration in the culture supernatant was measured using enzyme-linked immunosorbent assay(ELISA).Results In cultured primary rat hippocampal neurons,bilirubin exposure for 3 and 6 h caused significant increases in the expressions of NLRP3 and activated caspase-1 compared with those in the control group(P<0.05). Pretreatment of the cells with VX-765 obviously suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative survival rate of the neurons was(84.02±2.31)% in VX-765 intervention group,significantly higher than that in bilirubin group (P<0.05)but lower than that in the control group(P<0.05);LDH release rate in VX-765 intervention group was(10.78±1.58)%, significantly lower than that in bilirubin group(P<0.05)but higher than that in the control group(P<0.05).The cell death rate in VX-765 intervention group was(5.58±1.23)%,significantly lower than that in bilirubin group(P<0.05)but higher than that in the control group (P<0.05). Conclusion In cultured primary rat hippocampal neurons, caspase-1 activation plays a role in bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against bilirubin-induced neuronal injury by inhibiting caspase-1 activation.关键词
胆红素/神经毒性/海马神经元/caspase-1/VX-765Key words
bilirubin/neurotoxicity/hippocampal neurons/caspase-1/VX-765引用本文复制引用
韦倩,冯洁,何春梅,华子瑜..Caspase-1活化在胆红素诱导的大鼠海马神经元损伤中的作用[J].南方医科大学学报,2018,38(5):567-571,5.基金项目
国家自然科学基金(81200459) （81200459）
重庆市基础科学与前沿技术研究一般项目(CSTC2013jcyjA0020)Supported by National Natural Science Foundation of China(81200459). （CSTC2013jcyjA0020）
