~1H磁共振波谱对局灶性脑缺血大鼠脑内代谢物变化的定量评估(英文)

Quantitative evaluation of the changes of brain metabolits in rats with focal cerebral ischemia by using ~1H magnetic resonance spectrum

背景:脑缺血后脑内代谢物会出现异常变化。目的:通过1H磁共振波谱动态观察局灶性脑缺血大鼠脑内一系列生化代谢的改变,客观反映脑缺血恢复期脑内代谢产物的变化规律。设计:随机对照实验。单位:重庆医科大学附属第一医院的神经内科和放射科。材料:实验于2004-04/07在重庆医科大学附属第一医院放射科完成,选择成年Wistar清结级大鼠24只。随机分为对照组,假手术组和脑缺血组,每组8只。方法:脑缺血组以右侧颈内动脉栓塞制作局灶性脑缺血模型。假手术组栓塞线仅插入颈内动脉未深及大脑中动脉的起始处,对照组麻醉后不作任何处理。应用GEsignaHighspeedMRI1.5T超导磁共振波谱仪,缺血组和假手术组于术后30min,1,3,6,12,24h,3,7,15d,1,2个月对脑梗死区域和对侧半球相应区域进行代谢物的波谱分析。对照组也在上述相应的时间点进行检查。主要观察指标:脑梗死区域和对侧半球相应区域乳酸、N-乙酰天冬氨酸、胆碱及肌酸代谢物的变化。结果:参加实验的动物24只,假手术组中途因麻醉过量死亡2只,脑缺血组因脑缺血后严重脑水肿死亡4只,进入结果分析18只大鼠,正常对照组8只,假手术组6只,脑缺血组4只。①正常对照组和假手术组双侧代谢物无异常改变,分布对称。②脑缺血组梗死区N-乙酰基天冬氨酸、胆碱和肌酸均于脑缺血后30min开始升高,3～6h逐渐降低,但梗死区与对照区N-乙酰基天冬氨酸、胆碱和肌酸没有明显差别(P>0.05)。③6h时患侧的N-乙酰基天冬氨酸显著降低,24h达最低水平(45.21±0.37),胆碱和肌酸于3d降到最低(胆碱93.80±0.56,肌酸69.33±0.44),随缺血时间的延长,N-乙酰基天冬氨酸,胆碱和肌酸逐渐增加,尤其是N-乙酰基天冬氨酸增加最明显,2个月时N-乙酰基天冬氨酸较24h增加2.5倍(112.00±0.03,45.21±0.37,t=-3.33,P<0.05)。④患侧最早于脑缺血后10min检测到乳酸(47.27±0.21),随缺血时间的推移,脑梗死区与对应区乳酸均持续增加到1d以上,12h达高峰,3d开始减少,脑梗死区乳酸明显高于对侧(66.83±0.43,44.35±0.35,t=2.739,P<0.05),在1,2个月时乳酸没有再次升高。结论:①1H磁共振波谱能在患侧脑缺血后10min检测到乳酸,可及早反映动物脑缺血后脑内代谢产物的改变。②1H磁共振波谱能客观定量化反映脑缺血恢复期脑内代谢物的异常。

BACKGROUND： Brain metabolic abnormality can be observed after cerebral ischemia. OBJECTIVE： To observe the changes of biochemical metabolism of rats with focal cerebral ischemia with ^1H magnetic resonance spectroscopy （MRS） in order to reflect the metabolite abnormalities of rats during cerebral ischemic recovery phase. DESIGN： Randomized controlled study. SETTING： Departments of Neurology and department of Radiology of First Affiliated Hospital of Chongqing Medical University. MATERIALS： The experiment was conducted at the Radiological Department of First Affiliated Hospital of Chongqing Medical University from April to July 2004. Totally 24 adult Wistar rats with clean grade were randomly divided into three groups, namely： control group, sham operation group and cerebral ischemia group, with 8 rats in each group. METHODS： The focal cerebral ischemic model was established by occluding the right internal carotid artery in cerebral ischemia group and the filament were just inserted into the internal carotid artery not into the middle cerebral artery in sham operation group, nothing was done except for anesthetizing in the control group.^1H MRS was performed within the area of cerebral infarction and the homologous area of the contralateral hemisphere using 1.5T GE sigMa Highspeed MRI spectrometer in cerebral ischemic and shamed operation group at the following time point of 30 minutes, 1, 3, 6, 12, 24 hours, 3, 7, 15 days, 1 and 2 months after cerebral ischemia, and in the control group at the same time point. MAIN OUTCOME MEASURES： Changes of lactate, N-acetyl-aspartate （NAA）, choline and creatine in infarct hemisphere and contralateral hemisphere. RESULTS： Totally 24 rats were selected in the study, but two died of anesthesia in sham operation group and four of serious brain edema in cerebral ischemia group, only 18 rats entered the final analysis with 8 in normal control group, 6 in sham operation group and 4 in cerebral is- chemia group.① In the normal and the sham operation group, bilateral metabolites were symmetrically distributed, no significant differences.② The marked increase in NAA, choline and creatine was recognizable in bilateral spectra 30 minutes after cerebral ischemia and decreased to the period of 3-6 hours, but there was no significant difference in NAA, choline and creatine between two hemispheres （P 〉 0.05）.③ NAA was decreased at 6 hours and reached the lowest level at 24 hours （45.21±0.37）, choline （93.80±0.56） and creatine （69.33±0.44） at 3 days, and then NAA, choline and creatine gradually increased over time. The increase in NAA was especially obvious which increased by 2.5 times at 2 months than that at 24 hours after cerebral ischemia （112.00±0.03, 45.21±0.37, t=-3.33, P〈 0.05）.④ The earliest detection of lactate was at 10 minutes within the infarct. The lactate concentration elevated at 1 day and peaked at 12 hours, and a partial recovery of the reduction of lactate was seen at 3 days, and the lactate increase within the infarct region was significant compared with that of the homologous area （66.83±0.43,44.35±0.35, t=2.379, P 〈 0.05）. However, the elevation in lactate was no longer observed during the period of up to 2month follow-up. CONCLUSION：①^1H MRS can detect lactate after 10-minute cerebral ischemia and reflect the metabolites changes in brain of rats after cerebral ischemia. ②^1H MRS can reflect the metabolite abnormality during the cerebral ischemic recovery phase objectively.