Zhang Qibin, Hu Jian Zhi, Rommereim Donald N, Murphy Mark K, Phipps Richard P, Huso David L, Dicello John F
Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
Radiat Res. 2009 Nov;172(5):607-16. doi: 10.1667/RR1715.1.
Herein we demonstrate that high-resolution magic angle spinning (MAS) 1H NMR can be used to profile the pathology of bone marrow rapidly and with minimal sample preparation. The spectral resolution obtained allows several metabolites to be analyzed quantitatively. The level of NMR-detectable metabolites in the epiphysis + metaphysis sections of mouse femur were significantly higher than that observed in the diaphysis of the same femur. The major metabolite damage to bone marrow resulting from either 3.0 Gy or 7.8 Gy of whole-body gamma radiation 4 days after exposure were (1) decreased total choline content, (2) increased fatty acids in bone marrow, and (3) decreased creatine content. These results suggest that the membrane choline phospholipid metabolism (MCPM) pathway and the fatty acid biosynthesis pathway were altered as a result of radiation exposure. We also found that the metabolic damage induced by radiation in the epiphysis + metaphysis sections of mouse femur was higher than that of the diaphysis of the same femur. Traditional histopathology analysis was also carried out to correlate radiation damage with changes in metabolites. Importantly, the molecular information gleaned from high-resolution MAS 1H NMR complements the pathology data.
在此,我们证明高分辨率魔角旋转(MAS)1H NMR可用于快速分析骨髓病理,且样品制备最少。所获得的光谱分辨率允许对几种代谢物进行定量分析。小鼠股骨骨骺+干骺端切片中NMR可检测代谢物的水平显著高于同一股骨骨干中观察到的水平。全身γ射线照射3.0 Gy或7.8 Gy后4天,对骨髓造成的主要代谢物损伤为:(1)总胆碱含量降低;(2)骨髓中脂肪酸增加;(3)肌酸含量降低。这些结果表明,辐射暴露导致膜胆碱磷脂代谢(MCPM)途径和脂肪酸生物合成途径发生改变。我们还发现,辐射对小鼠股骨骨骺+干骺端切片诱导的代谢损伤高于同一股骨骨干。还进行了传统组织病理学分析,以将辐射损伤与代谢物变化相关联。重要的是,从高分辨率MAS 1H NMR收集的分子信息补充了病理数据。