[1]韦倩,冯洁,何春梅,等.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,(05):567.
 Role of caspase- activation in bilirubin-induced injury in cultured primary rathippocampal neurons.[J].Journal of Southern Medical University,2018,(05):567.
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Caspase-1活化在胆红素诱导的大鼠海马神经元损伤中的作用()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年05期
页码:
567
栏目:
出版日期:
2018-05-15

文章信息/Info

作者:
韦倩冯洁何春梅华子瑜
Author(s):
Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons
关键词:
胆红素神经毒性海马神经元caspase-1VX-765
Keywords:
bilirubin neurotoxicity hippocampal neurons caspase-1 VX-765
摘要:
目的研究半胱氨酸天冬氨酸蛋白酶-1(caspase-1)活化及VX-765在胆红素诱导大鼠海马神经元损伤中的作用。方法原 代培养大鼠海马神经元分为胆红素组、对照组、VX-765组;胆红素组给予胆红素(50 μmol/L),对照组给予同体积药物溶剂二甲 基亚砜(DMSO),VX-765组在胆红素干预前1 h给予VX-765(50 μmol/L);Western blot检测NLRP3、活化caspase-1表达,改良 MTT、乳酸脱氢酶(LDH)释放率及台盼蓝染色检测细胞相对存活率及死亡率,ELISA法检测原代培养上清IL-18 水平。结果 胆红素诱导原代培养大鼠海马神经元3、6 h,NLRP3、活化caspase-1蛋白表达明显高于对照组(P<0.05)。VX-765干预后,活化 caspase-1表达与胆红素组相比明显降低(P<0.05)。分组干预细胞24 h,VX-765组的相对存活率为(84.020±2.311)%,明显高于 胆红素组(P<0.05),低于对照组(P<0.05);VX-765组LDH释放率为(10.780±1.577)%,明显低于胆红素组(P<0.05),高于对照组 (P<0.05);VX-765组台盼蓝染色阳性率为(5.580±1.234)%,明显低于胆红素组(P<0.05),高于对照组(P<0.05)。结论在原代 培养的大鼠海马神经元中,caspase-1活化参与胆红素神经毒性的发生,VX-765抑制其活化发挥神经保护作用。
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.

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更新日期/Last Update: 1900-01-01