新生猪缺氧缺血脑损伤后基底节乳酸代谢及其转运体表达的研究

摘要

目的 通过1H-MRS在体检测新生猪缺氧缺血脑损伤(HIBI)模型在损伤后不同时间点乳酸含量的变化并与乳酸转运体(MCT-2、MCT-4)的表达特征进行相关研究,以期进一步明确乳酸在HI后脑损伤中的作用机制.材料与方法 选用出生后3～5 d的健康新生猪,体重约为1～1.5 kg,对照组5头,HIBI模型组30头.通过1H-MRS成像检测缺氧缺血后不同时间点基底节区乳酸的变化并与MCT-2、MCT-4的表达进行相关分析,P＜0.05认为差异有统计学意义.结果 (1)1H-MRS结果显示,HIBI后Lac峰值出现在2～6 h,随后Lac逐渐下降,逐步降低至与对照组水平相当.除24～48 h、48～72 h与对照组差异无统计学意义(P=0.86、0.26)外,其余模型组与对照组差异均有统计学意义(P＜0.05).(2)MCT-2、MCT-4在HI后表达先上调后降低,均在12～24 h达到高峰,与其余组均有统计学差异(P＜0.05).结论 缺氧缺血后,乳酸含量的变化可调节神经元及胶质细胞乳酸相关转运体的表达.%Objective:To investigate the expression characteristics of lactate and associated transporters in basal ganglia following hypoxic-ischemic reperfusion brain injury in a piglet model.Materials and Methods:A total of 35 healthy piglets (3-5 days old,1.0-1.5 kg) were selected.They were divided into control (n=5) and hypoxic-ischemic (HI) model groups (n=30).The HI model group was further divided into six groups according to 1H-magnetic resonance spectroscopy (1H-MRS)scan times after HI (0-2 h,2-h,6-12 h,12-24 h,24-48 h and 48-72 h;n=5/group).The HI model was established by bilateral common carotid artery occlusion and simultaneous hypoxia treatment for 40 min.Piglets in the control group received the same surgical procedure without the hypoxia-ischemia process.1H-MRS imaging was performed at various time points after HI.The right basal ganglia was the region of interest (ROI) in 1H-MRS imaging for which data was processed by LcModel software.Animals were euthanized immediately after the last scan and the whole brain was quickly removed and bilateral hemispheres separated.The right hemisphere was used for the pathological examination and immunohistochemical staining of monocarboxylate transporters (MCTs).ANOVA analyses were conducted.P＜0.05 represented statistical significance.Results:(1) The lactate level became reduced after an initial increase,with the maximal level occurring around 2-6 h following HI.(2) The expression of both MCT-2 and MCT-4 in the basal ganglia initially reached a peak value at 12-24 h and decreased thereafter and they were significantly different at 12-24 h after HI compared to the control group and the other time points of the HI model group (P＜0.05).Conclusions:These results indicate that lactate content has potential to regulate the expression of its related transporters in neuronal and glial cell and they have a synergistic effect on the energy metabolism following hypoxic-ischemic reperfusion brain injury.