阿尔茨海默病大鼠氢质子磁共振波谱研究  

~1H-proton magnetic resonance spectroscopy features of Alzheimer's disease model in rats

作　　者：林富春 杨期东[2] 何建川[3] 游箭[3] 邵志成 马海涵[2] 邵阳[1,2,3] LIN Fuchun YANG Qidong HE Jianchuan YOU Jian SHAO Zhicheng MA Haihan SHAO Yang(Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008, China Sichuan Key Lab of Medical Imaging, North Si- chuan Medical College, Nanchong 637000, China)

机构地区：[1]南京医科大学第二附属医院神经内科,江苏南京210011 [2]中南大学湘雅医院神经内科,湖南长沙410008 [3]川北医学院医学影像四川省重点实验室,四川南充637000

出　　处：《中国医学物理学杂志》2017年第10期1073-1077,共5页Chinese Journal of Medical Physics

基　　金：四川省杰出青年学科带头人培养基金(05ZQ026-020);四川省科技攻关项目(05SG0485)

摘　　要：目的:探讨海马注射β-淀粉样肽(Aβ1-42)诱发阿尔茨海默病(AD)大鼠模型的病理学变化及氢质子磁共振波谱(~1H MRS)特性。方法:健康SD大鼠40只,实验随机分为假伤组(Sham组)、阿尔茨海默病模型(AD组)。采用大鼠海马注射Aβ_(1-42)复制AD模型。苏木精-伊红染色法染色观察海马CA1区神经元形态,免疫化学染色观察Aβ的沉积,采用Morris水迷宫法进行大鼠记忆功能的测定。~1H MRS检测AD鼠脑中的N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)和乳酸(Lac)水平。结果:与Sham组比较,AD组游全程时间延长,错误次数增加,差异显著(均P<0.01)。与Sham组比较,AD组双侧海马CA1区神经元数目减少,核固缩增加;且与注射对侧比较,Aβ_(1-42)注射侧大鼠海马CA1区神经元数目显著减少,核固缩显著增加。免疫化学染色Sham组呈阴性;AD组双侧抗Aβ1-42呈阳性,且与注射对侧比较,注射侧阳性显著增加。~1H MRS结果Sham组双侧半球无显著性差异。与Sham组比较,AD组双侧~1H MRS海马NAA/Cr明显降低、Cho/Cr增加、Lac/Cr增加;在AD组,与注射对侧半球比较,注射侧半球海马NAA/Cr明显降低(P<0.05)、Cho/Cr显著增加(P<0.01)、Lac/Cr显著增加(P<0.01)。结论:Aβ1-42能引起大鼠海马CA1区神经元损伤,记忆功能下降,注射Aβ后4周NAA/Cr已有明显改变,与免疫组化发现Aβ1-42表达增强结果一致,提示利用~1H MRS检测NAA/Cr改变,可能有助于AD早期临床诊断。Objective To investigate the pathological changes and ^1H-proton magnetic resonance spectroscopy（ ^1H MRS） features of experimental rat injected with Aβ（1-42） in hippocampus to induce Alzheimer＇s disease（AD）. Methods Forty healthy Sprague Dawley（SD） rats were randomly divided into Sham group and AD group. The SD rats in AD group were injected with Aβ（1-42） in hippocampus to induce AD, while the SD rats in Sham group were injected with normal saline. The morphology of neurons in hippocampus CA1 area was observed with hematoxylin-eosin（HE） staining; the deposition of Aβ was assessed by immunochemical staining; the memory function was evaluated by Morris water maze. Herein, we used -1H MRS images to evaluate the levels of NAA, Cho, Cr and Lac in the brains of AD rats. Results Compared with those in Sham group, the abilities of learning and memory in AD group were reduced for the rats in AD group extended their time for swimming the whole process and increased the mistake times（P〈0.01）. Under microscopy, AD group displayed obviously decreased number of neurons and higher karyopyknosis rate in the hippocampus CA1 area as compared with Sham group. Within AD group, the number of neurons in the hippocampus CA1 area was significantly lower and karyopyknosis rate was higher in the injected lateral as compared with contra-lateral.Immunohistochemical staining was negative for Aβ1-42 in Sham group, but positive in AD group. In AD group, the injected lateral showed a higher positive rate of Aβ1-42 than the contralateral. ^1H MRS revealed that no significant difference was found in the level of compounds（NAA, Cho, Cr and Lac） between two laterals in Sham group. Compared with Sham group, AD group showed a decrease in NAA/Cr, and increases in Cho/Cr and Lac/Cr. Within AD group, the comparison demonstrated that the injected lateral had a decrease in NAA/Cr（P〈0.05） and increases in Cho/Cr（P〈0.01） and Lac/Cr（P〈0.01）. Conclusion Aβ1-42 could cause significant injury to neuro

关 键 词：阿尔茨海默病 Β-淀粉样肽 氢质子磁共振波谱 

分 类 号：R749.16[医药卫生—神经病学与精神病学]