摘要
目的基于多模态影像学结合多种组织学技术可视化评估早产脑缺氧缺血后大鼠脑代谢微环境变化,并探讨脑内乳酸代谢异常对少突胶质前体细胞的影响,为早产儿脑白质损伤(PWMI)的早期诊疗提供依据。材料与方法SPF级健康3日龄SD新生大鼠36只,采用随机数字表法分为假手术(Sham)组与模型(PWMI)组,每组18只。通过缺氧缺血法建立新生大鼠PWMI模型。建模后24 h,采用激光散斑成像监测脑血流血氧变化;通过多模态影像学观察PWMI情况及脑内微环境改变;HE染色观察脑白质区神经细胞形态学改变;酶联免疫吸附法检测脑白质区乳酸含量及乳酸脱氢酶活性变化。采用免疫荧光染色观察新生大鼠PWMI后室管膜下区少突胶质前体细胞数的动态变化。结果建模后24 h,多模态影像学结果显示,PWMI组损伤侧T2WI及扩散加权成像呈高信号,相对脑血流量、相对血氧饱和度、胼胝体区和纹状体区相对表观扩散系数及酰胺质子转移洛伦兹差分值均低于Sham组(t=29.466、23.522、59.006、54.778、10.263,P均<0.001),乳酸含量高于Sham组(t=-7.521,P<0.001)。HE染色及酶联免疫吸附测定结果显示,PWMI组损伤侧脑白质区神经细胞排列疏松紊乱;乳酸含量及乳酸脱氢酶活性高于Sham组(t=-6.079、-10.548,P均<0.001)。免疫荧光染色结果显示,PWMI组损伤侧室管膜下区PDGFR-α+细胞数在建模后24 h高于Sham组,建模后11 d低于Sham组(t=-8.386、6.676,P均<0.001)。室管膜下区少突胶质前体细胞数与酰胺质子转移洛伦兹差分值呈正相关(r=0.821,P=0.0011),与脑内乳酸含量呈负相关(r=-0.880,P=0.0002)。结论多模态影像学可活体监测新生大鼠PWMI早期脑内代谢变化,尤其是乳酸变化,为其早期诊断提供可视化依据;早产脑缺氧缺血后脑内乳酸水平升高,抑制少突胶质前体细胞发育,可能是PWMI的重要原因。
Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-αimmunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.0011),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.0002).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.
作者
张孝祖
张海默
王怡静
鞠涛
秦佑成
刘畅
于淼
张春磊
王晓莉
ZHANG Xiaozu;ZHANG Haimo;WANG Yijing;JU Tao;QIN Youcheng;LIU Chang;YU Miao;ZHANG Chunlei;WANG Xiaoli(School of Medical Imaging,Shandong Second Medical University,Weifang 261053,China;不详)
出处
《中国医学影像学杂志》
北大核心
2025年第5期501-506,共6页
Chinese Journal of Medical Imaging
基金
国家自然科学基金(82071888)
山东省自然科学基金(ZR2024MH067)
2019年高等学校青创人才引育计划
山东省医药卫生科技项目(202406031122)。
