全脑辐照致神经损伤大鼠神经化学物质类生物标志物的筛选

Screening of Neurochemical Biomarkers for Rats with Nerve Injury Induced by Whole-Brain Irradiation

为了对全脑辐照诱导神经损伤后的大鼠血进行外周血中神经化学物质类生物标志物的筛选,采用前期建立的血清中神经化学物质的化学衍生-超高效液相色谱-串联质谱分析方法,对不同全脑辐照剂量(0、10、30 Gy)和分次累积辐照(10 Gy×3)大鼠血清中42种神经化学物质的浓度进行了测定并进行了基于靶向代谢组学策略的统计学分析.单变量统计分析结果表明,辐照组(10、30、10 Gy×3)中去甲肾上腺素、乙酰胆碱、γ-氨基丁酸、酪胺、谷氨酸、酪氨酸、色氨酸、褪黑素、α-丙氨酸和甘氨酸的含量显著(p<0.05)低于对照组(0 Gy),而乙酰胆碱和褪黑素的浓度变化趋势相反(p<0.05).同时发现10 Gy×3组中神经化学物质含量的变化程度低于30 Gy组,表明分次累积辐照造成的神经化学物质扰动程度较同剂量的单次辐照低;通过结合多变量统计OPLS-DA模型分析中的变量重要性投影(VIP)值,本研究筛选出乙酰胆碱、谷氨酸、酪胺和褪黑素(p<0.05,VIP>1)可作为全脑辐照诱导神经损伤的潜在生物标志物.

Screening of neurochemical biomarkers was performed in peripheral blood serum from rats with nerve injury induced by whole-brain irradiation(WBI).Serum of rats treated with different doses of WBI(0,10,and 30 Gy)and fractional cumulative radiation(10 Gy×3)were determined for the concentration of 42 neurochemicals using the previously established chemical derivatization and ultra-high performance liquid chromatography-tandem mass spectrometry method followed by statistical analysis based on targeted metabolomics.Univariate statistical analysis indicated that the concentrations of norepinephrine,acetylcholine,γ-aminobutyric acid,tyramine,glutamic acid,tyrosine,tryptophan,melatonin,α-alanine,and glycine were significantly(p<0.05)lower than the control group(0 Gy),while the concentrations of acetylcholine and melatonin changed in the opposite trend(p<0.05);Meanwhile the variation degree of neurochemicals in the 10 Gy×3 group was found lower than that in the 30 Gy group,indicating that the disturbance degree of neurochemicals caused by cumulative irradiation was lower than that caused by single irradiation of the same dose.Combining with the variable importance in the projection(VIP)in the multivariate statistical OPLS-DA model,the proposed method has selected acetylcholine,glutamate,tyramine,and melatonin as the potential biomarkers for the nerve injury induced by WBI.