双环己酮草酰二腙诱导小鼠模型行为学检测及脑代谢物变化的意义  

Behavioral and neurochemical alterations in mice exposed to cuprizone

作　　者：延根[1] 贾岩龙[1] 章桃 聂婷婷[1] 玄英花[1] 吴仁华[1] 

机构地区：[1]汕头大学医学院第二附属医院放射科,515041

出　　处：《中华诊断学电子杂志》2015年第1期42-46,共5页Chinese Journal of Diagnostics(Electronic Edition)

基　　金：国家自然科学基金(30930027)

摘　　要：目的探讨双环己酮草酰二腙(CPZ)诱导小鼠模型行为学检测及脑代谢物变化的意义。方法 20只8周龄雄性C57BL/6小鼠,分成CPZ处理组(n=10)、空白对照组(n=10),饲养于温度(22±1)℃明暗各12 h环境中。CPZ处理组给予0.2%(质量分数)CPZ混合鼠饲料连续4周,饮用纯净水;空白对照组给予正常鼠饲料,同样饮用纯净水。两组动物均行旷场实验和Y迷宫行为学检测实验、氢质子磁共振波谱(1HMRS)和T2WI检查。所有数据均用SPSS 15.0统计软件包处理,T2强度与脑脊液的比值及脑代谢物水平用独立样本t检验。结果 CPZ处理组小鼠在中央区活动的路程较空白对照组长[(295.430±83.250)cm,(257.440±75.430)cm,t=0.031,P<0.05];两组T2WI侧脑室体积视觉定量分析中,CPZ组侧脑室体积[(0.980±0.050)mm2]大于空白对照组[(0.890±0.470)mm2],差异有统计学意义(t=5.670,P<0.05)。T2强度与脑脊液比值:CPZ组均高于空白对照组,大脑皮层(0.787±0.015,0.628±0.027,t=0.880,P<0.05)、尾状核区(0.732±0.012,0.628±0.021,t=0.003,P<0.05)和海马区(0.745±0.021,0.620±0.022,t=0.027,P<0.05)差异有统计学意义;丘脑区CPZ组增高,但差异无统计学意义(0.602±0.016,0.562±0.019,t=0.378,P>0.05)。频谱结果显示,CPZ组CPU区神经元标志物N-乙酰天冬氨酸(4.217±0.488)和其化合物天冬氨酸和乙酰天冬氨酰谷氨酸化合物(4.236±0.389)、谷氨酸类化合物(5.147±0.477)及短TE序列兴奋性神经递质谷氨酸绝对水平比空白对照组明显下降,差异有统计学意义(t=9.014,10.990,7.307;P<0.05)。丘脑区主要位于3.05 ppm的与能量代谢有关的肌酸和磷酸肌酸化合物浓度(4.415±0.527)和与胶质细胞增生有关的肌醇绝对水平(3.737±0.428)在CPZ组明显下降且差异有统计学意义(t=9.120,5.911;P<0.05);其余测到的脑代谢物水平差异无统计学意义(P>0.05)。讨论CPZ处理组小鼠显示焦虑样行为异常改变及脑白质损伤,并且CPZ处理过程中出现能量代谢及神经�Objective To investigate the behavioral and neurochemieal alterations in mice exposed to cuprizone.Methods C57BL/6 mice were given 0.2% CPZ-containing diet for 4 weeks while controls ate the same diet without CPZ.The animals were subjected to behavioral tests,T2WI and 1HMRS scan.At/ultra short echo stimulated echo acquisition （STEAM） localization sequence （ TR/TM/TE = 5 000/10/2.2 ms ） was used to measure in vivo proton spectra from the left striatum （voxel volume：8 μL） and thalamus （27 L） of C57BL/6 mice at 7.0T and acquired proton spectra post-processed offline with LCModel.The difference of the T2WI signal intensity was compared with independent sample t -test, and the difference of neurochemical alterations was compared with one-way analysis of variance. Results CPZ-fed mice showed significant decrease of spontaneous alternation in the Y-maze test [ 295.430 ± 83.250） cm, （ 257.440 ± 75.430） cm, t = 0.031, P〈0.05] .In quantitative analysis of visual,lateral ventricle volume in CPZ-fed mice was larger than that in control mice, and the difference was statistically significant [ （ 0. 980 ± 0.050 ） mm2, （ 0. 890 ± 0.470）mrn2, t =5.670, P 〈0.05].The signal of intensity in the CTX（0.787±0.015,0.628_±0.027） ,CPU （0.73220.012,0.628±0.021） and Hip （0.745±0.021,0.620±0.022） were significantly high in CPZ-fed mice（ t = 0.880,0.003,0.027 ; P 〈0.05） .The concentrations of N-acetyl aspartate （ NAA, 4.21720.488）, N-acetyl aspartate ± N-acety laspartyl glutamate （NAA± NAAG, 4.236± 0.389） in the left striatum and thalamus were significantly reduced in CPZ-fed mice （t = 9.014, 10.990; P 〈0.05）. In addition, the concentration of Glu±Gln （ 5.147 ± 0.477, t = 7.307, P 〈 0.05 ） in the left thalamus of CPZ-fed mice was significantly lower than that in control mice.The concentrations of Cr±PCr （4.41520.527） and MI （3.737± 0.428） in thalamus were significantly reduced in CPZ-fed mice（ t = 9.120,5.911; P 〈0.05）.There were no satiti

关 键 词：铜宗 脱髓鞘 磁共振频谱学 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]