首页|乌头碱运动神经毒性及miR-124作为其潜在毒性标志物的探索研究

乌头碱运动神经毒性及miR-124作为其潜在毒性标志物的探索研究

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目的 研究循环微RNA(microRNA,miR)-124成为乌头碱运动神经毒性标志物的潜力.方法 将42只大鼠随机分为对照组、乌头碱0.025 mg/kg(低剂量)组及0.05 mg/kg(高剂量)组,每组14只,静脉注射给药14 d.采用功能观察组合检测运动行为改变;观察脑组织病理和检测脑细胞凋亡;采用实时荧光定量聚合酶链式反应检测脑和血液miR-124表达;采用酶联免疫吸附试验检测血液神经元特异性烯醇化酶(neuron-specific enolase,NSE)和胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)的含量.结果 与对照组相比,低剂量组给药D14后、高剂量组给药D1和D14后出现移笼较容易、头部或躯体运动减少以及反射减弱等运动行为改变(P<0.05);高剂量组见大脑纹状体坏死和胶质细胞异常增生;低、高剂量组小脑颗粒细胞层和大脑皮层细胞凋亡增加,脑组织miR-124表达增加(P<0.01).D1给药后1 h,高剂量组循环miR-124的升高最早(P<0.01);D1给药后8 h,高剂量组循环NSE及GFAP水平升高最早(P<0.01).结论 与循环NSE和GFAP相比,高剂量组循环miR-124更早出现升高,具有检测乌头碱运动神经毒性的潜力.
Study on motor neurotoxicity of aconitine and miR-124 as a potential toxicity marker
Objective To investigate the potential of circulating microRNA(miR)-124 as a marker of motor neurotoxicity of aconitine.Method Forty-two rats were randomly divided into control group,aconitine 0.025 mg/kg(low dose)group and aconitine 0.05 mg/kg(high dose)group,14 rats in each group,and were given intravenous injection for 14 days.Functional observation combination was used to detect the change of motor behavior.The pathology of brain tissue was observed.The apoptosis of brain cells was detected.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of miR-124 in brain and blood.The levels of neuron-specific enolase(NSE)and glial fibrillary acidic protein(GFAP)in blood were detected by enzyme-linked immunosorbent assay.Results Compared with the control group,the motor behavior of D14 in low dose group and D1 and D14 in high dose group showed easier cage movement,reduced head or body movement,and weakened reflexes after administration(P<0.05).Brain striatum necrosis and glial cell dysplasia were observed in high dose group.The apoptosis of cerebellar granule cell layer and cerebral cortex was increased in low dose and high dose groups,and the expression level of miR-124 in brain tissue was increased(P<0.01).The increase of circulating miR-124 was the earliest in high dose group at 1 h after Dl administration(P<0.01).At 8 h after D1 administration,the increase of circulating NSE and GFAP in high dose group was the earliest(P<0.01).Conclusion Compared with circulating NSE and GFAP,circulating miR-124 increased earlier in high dose group,which has the potential to detect the motor neurotoxicity of aconitine.

aconitinetoxicity marker of motor neurotoxicityneuron-specific enolaseglial fibrillary acidic proteinmicroRNA-124

周慧、杨鑫、汪溪洁、马璟

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中国医药工业研究总院,上海 201203

上海益诺思生物技术股份有限公司,上海 201203

乌头碱 运动神经毒性标志物 神经元特异性烯醇化酶 胶质纤维酸性蛋白 微RNA-124

上海市科委研发平台专项

21DZ2291000

2024

世界临床药物
上海医药工业研究院

世界临床药物

CSTPCD
影响因子:0.849
ISSN:1672-9188
年,卷(期):2024.45(6)