电针对帕金森病模型小鼠纹状体背侧的c-Fos表达的选择性调节

目的 观察电针对帕金森病(Parkinson’s disease, PD)模型小鼠纹状体内原癌基因蛋白(c-Fos)表达的选择性调控作用,以探究电针治疗PD的潜在机制。方法 制备6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)右侧损伤的PD模型小鼠,实验分为对照组、对照+电针组、模型组和模型+电针组。电针施加于小鼠下肢双侧的“足三里”和“三阴交”穴位,采用100 Hz电针刺激持续30 min,继而用免疫组化检测纹状体背侧、腹侧和扣带回皮质的c-Fos蛋白表达。结果 模型组小鼠右侧背部纹状体c-Fos表达较对照组显著降低(P<0.001),而电针刺激显著增加了模型组右侧背部和腹部纹状体的c-Fos的表达(P<0.05)。检测扣带回皮质的c-Fos表达,各组之间差异无统计学意义,电针未产生明显的调控作用。结论 电针可区域特异性地激活PD小鼠损伤侧纹状体背部神经元的活性。     

帕金森病大鼠脑局部葡萄糖代谢及多巴胺2型受体表达的microPET研究

目的 应用18F-FDG和11C-NMSP microPET评估大鼠帕金森病(PD)模型脑局部葡萄糖代谢及多巴胺2型受体(DRD2)表达的差别及意义.方法 采用6-羟多巴胺制备偏侧PD大鼠模型,2周后应用18F-FDG和11C-NMSPmicroPET扫描,比较PD模型组大鼠和对照组大鼠的脑局部葡萄糖代谢及DRD2表达,用免疫组化染色比较两组的酪氨酸羟化酶表达.结果 PD模型大鼠纹状体、海马、感觉运动皮质葡萄糖代谢率分别为88.2%±2.2%,94.5%±4.5%,96.2%±5.8%,显著低于对照组相应脑区92.7%±2.8%(P＜0.01),98.9%±3.9%(P＜0.01),102.8%±2.1%(P＜0.01);DRD2表达在PD模型的右侧纹状体为112.9%±9.0%,明显高于对照组102.3%±1.4%(P＜0.01).结论 PD模型大鼠损毁侧纹状体、海马、感觉运动皮质葡萄糖代谢均降低;而损毁侧纹状体DRD2表达明显升高.18F-FDG和11C-NMSP microPET能有效评估PD模型脑局部葡萄糖代谢及DRD2表达水平,可能成为早期诊断PD的分子影像学工具.

Abstract：

Objective To employ 18F-fluoro-2-aeoxyglucose (18 F-FDG) and (3-N-[11 C] methylspiperone ) 11C -NMSP microPET to assess the changes of regional cerebral glucose metabolism and the expression of dopamine receptor type 2 ( DRD2 ) in a rat model of Parkinson's disease (PD). Methods A hemiparkinsonian model was established in rats by unilateral pretreatment with 6-hydroxydopamine (6-OHDA). At 2 weeks after 6-OHDA insult, 18F-FDG and 11C-NMSP microPET scan were performed to compare the differences of regional cerebral glucose metabolism and the expression of DRD2 between the PD and control groups respectively. The immunohistochemical staining was used to detect the expression of tyrosine hydroxylase in two groups. Results In the PD model, the glucose metabolism rates were 88. 2% ± 2. 2%, 94. 5% ±4.5% and 96. 2% ±5. 8% respectively, in right striatum, hippocampus and sensorimotor cortex. And they were significantly lower than those in the control group [ 92. 7% ± 2. 8% ( P ＜ 0. 01 ),98.9% ±3.9% (P＜0.01) & 102.8% ±2. 1% (P＜0.01) ].The expression of DRD2 in right striatum was significantly higher in the PD group than that in the control group ( 112. 9% ± 9. 0% vs 102. 3% ± 1.4%, P ＜ 0. 01 ). Conclusion In the PD rats, glucose metabolism decreases in injured side striatum,hippocampus and sensorimotor cortex while and the expression of DRD2 increases in injured side striatum.18F-FDG and 11C-NMSP microPET can effectively assess the regional cerebral glucose metabolism and the expression of DRD2 in PD. They may serve as effective molecular imaging tools for an early diagnosis of PD.     

听觉中枢纯音处理偏侧性质子磁共振波谱研究

目的 利用质子磁共振波谱(proton magnetic resonance spectroscopy,1H-MRS)技术观察纯音刺激后正常人左右半球听皮层代谢物偏侧性变化.方法 12例健康受试者听皮层在纯音刺激前后各接受一次多体素磁共振波谱检查.刺激声音为声强90dB、频率1000Hz的正弦波纯音脉冲.观察双侧听皮层N-乙酰天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)、谷氨酰胺和谷氨酸(Glx)、GABA等代谢物的波峰变化,并进行半定量分析,比较刺激前后听皮层代谢物左右半球偏侧性变化.结果 纯音刺激后左侧听皮层NAA/(Cho+Cr)、GABA/Cr比值[分别为(1.28±0.14),(0.21±0.08)],高于刺激前[分别为(1.02±0.18),(0.10±0.05)],Glx/Cr比值[(0.03±0.02)]明显低于刺激前[(0.10±0.04)],差异均有统计学意义(P<0.05);右侧听皮层刺激后NAA/(Cho+Cr)、Glx/Cr比值[分别为(0.92±0.13),(0.09±0.05)]均高于刺激前[分别为(0.90±0.11),(0.08±0.03)],但差异无统计学意义(P>0.05);GABA/Cr比值[(0.01±0.11)]明显低于刺激前[(0.11±0.07)],差异有显著性(P<0.002),纯音刺激后双侧听皮层Glx/Cr比值呈明显的非对称性.结论 纯音刺激后双侧听皮层代谢存在半球非对称性,可能为功能的非对称性提供生化方面的信息.

Abstract：

Objective To explore the asymmetry of metabolic products of the auditory cortex in normal human brain after being stimulated by the pure tone with the proton magnetic resonance spectroscopy(1 H-MRS). Methods Twelve healthy volunteers, including 7 males and 5 females, were performed MRS tests before and after the stimulation of the pure tone of 90 dB in intensity and 1000 Hz in frequency. The the metabolites peak of the N-acetylaspartate (NAA) ,creatine(Cr) ,choline( Cho) , glutamine/glutamate ( Glx) and GABA in auditory cortex were investigated, The content of metabolic products were conducted with half-quantitative analysis. The differences of the NAA/( Cho + Cr) ,Glx/Cr and GABA/ Cr ratios before and after pure tone stimulation in the bilateral auditory cortex were analyzed. The difference of distribution of the metabolic products between the left and right auditory cortex was also analyzed to explore the asymmetry of the auditory cortex. Results The NAA/( Cho + Cr) and GABA/Cr ratios increased,the Glx/Cr ratio decreased in the left auditory cortex after being stimulated by the pure tone. There were significant differences in the NAA/( Cho + Cr) , Glx/Cr and GABA/Cr ratios before and after pure tone stimulation (P<0.05) ;the GABA/Cr ratio decreased,the Glx/Cr and NAA/( Cho + Cr) ratios increased in the right auditory cortex after being stimulated by the pure tone, and statistical difference of the GABA/Cr ratio was found before and after pure tone stimulation (P<0. 05) ,however the difference of the Glx/Cr and NAA/(Cho + Cr) ratios before and after pure tone stimulation was not significant (P>0.05). There were statistically significant differences in the Glx/Cr ratio of the auditory cortex between two sides after being stimulated by the pure tone. Conclusion The metabolic lateralization exists in auditory cortex of normal human brain after being stimulated by the pure tone, which may be the bases of the functional asymmetry.     

神经降压素对帕金森病模型大鼠纹状体DA含量影响

目的观察神经降压素(NT)对正常和帕金森病模型大鼠纹状体多巴胺(DA)及其代谢产物含量的影响。方法采用6-羟基多巴胺(6-OHDA)单侧损毁内侧前脑束制备帕金森病大鼠模型。将5μL 1 mmol/L NT或生理盐水双侧缓慢注入正常及帕金森病模型大鼠侧脑室30 min后,利用高效液相色谱分析(HPLC)法检测纹状体DA及其代谢产物高香草酸(HVA)和3,4-二羟基苯乙酸(DOPAC)含量的变化。结果正常大鼠NT组纹状体DA含量与生理盐水组相比均明显升高(t=5.32,P<0.01)。帕金森病模型大鼠生理盐水组损毁侧纹状体DA含量与未损毁侧和正常大鼠生理盐水组相比明显降低(F=61.23,P<0.001);损毁侧纹状体DA更新率(DOPAC+HVA)/DA、DOPAC/DA、HVA/DA均明显高于未损毁侧和正常大鼠生理盐水组(F=27.52、21.12、28.43,P<0.001)。帕金森病模型大鼠侧脑室注射NT可明显提高两侧纹状体DA的含量(t=3.87、2.26,P<0.05)。结论 NT可增加正常及帕金森病模型大鼠纹状体DA的含量,提示NT具有抗帕金森病效应。     

Comparative study of D2 receptors and dopamine content in striatum before and after electro-acupuncture treatment in rats

Objective To evaluate the change in D(2) receptors and their relationship with dopamine (DA) content in experimental hemi-parkinsonism rats before and after electro-acupuncture (EA) treatment. Methods (125) Ⅰ-IBZM D(2) receptor cerebral autoradio-graphic analysis, HPLC-ECD detection of DA and its metabolites, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) were used to study their levels in striatum in pre-EA, EA and EA control group. Results The DA, HVA and DOPAC levels in striatum of the lesioned side in the EA group were elevated compared to the pre-EA and EA control group (P&lt;0.05). For the EA group, the striatum/cerebellum (125) Ⅰ-IBZM uptake ratio of the lesioned side was 8.04±0.71, (29.34%±4.83%) more than that of the contralateral side (P&lt;0.05), while no significant difference was observed as compared with that in the pre-EA group (8.09±0.52, 30.12%±4.53%, higher than that of the intact side P&gt;0.05). It was lower than the EA control group (8.61±0.63, P&lt;0.05), and the latter was (38.63%±3.71%) higher than that in its contralateral side (P&lt;0.05). Conclusion 6-OH-DA lesions in the substantia nigra and ventral tegmental areas induce an up-regulation of striatal D(2) binding sites. EA treatment could elevate the DA level of the lesioned side striatum and prevent D(2) receptor up-regulation in rats with experimental hemi-parkinsonism.     

电针对血管性痴呆大鼠学习记忆和血红素氧化酶的影响

[目的]探讨电针对血管性痴呆（VD）大鼠学习记忆障碍的治疗效应及其作用的分子机制.[方法]SD雄性大鼠60只,除假手术组10只外,其他大鼠均采用4-血管阻断法复制VD模型,存活大鼠随机分为电针组14只,尼莫通组13只,模型组13只;电针组针刺“百会”和“大椎”两穴,尼莫通组以12 mg/kg灌胃给药,假手术组与模型组未予任何治疗.采用Morris水迷宫观察治疗20d后各组大鼠在学习记忆方面的变化,并检测血红素氧化酶（HO）的蛋白表达和信使核糖核酸（mRNA）表达.[结果]与假手术组比较,模型组逃避潜伏期、HO-1蛋白表达、HO-1 mRNA表达增高（P＜0.01）;与模型组比较,电针组、尼莫通组逃避潜伏期、HO-1蛋白表达均显著减少（P＜0.01）,H0-1 mRNA表达水平均降低（P＜0.05）;电针组与尼莫通组比较,各指标均无显著性差异（P＞0.05）.[结论]电针治疗改善VD模型大鼠学习记忆能力与尼莫通治疗相仿,两法均可能与减少海马和皮质神经元细胞HO-1蛋白表达及H0-1 mRNA表达有关.     

淫羊藿苷脂质体经鼻给药对帕金森病大鼠行为学及神经递质的影响

目的观察经鼻给予淫羊藿苷脂质体对帕金森病模型大鼠的行为学症状及纹状体相关神经递质含量的影响。方法按随机原则选16只大鼠为假手术组(假手术/in组),另将64只造模成功的PD大鼠分为PD模型组(PD/in组)、淫羊藿苷脂质体经鼻给药组(ICA-PGL/in组)、淫羊藿苷经鼻给药组(ICA/in组)、淫羊藿苷脂质体静脉注射给药组(ICA-PGL/iv组),每组16只。药物持续干预2周后,通过检测大鼠阿扑吗啡旋转次数、圆筒实验、纹状体区TH表达以及相关神经递质含量的改变来观察淫羊藿苷脂质体结合经鼻给药方式对帕金森病模型大鼠的疗效。结果淫羊藿苷各治疗组运动功能较PD/in组有不同程度的改善,纹状体区双侧TH阳性纤维表达及纹状体区右侧单胺类神经递质DA、DOPAC和HVA含量较PD/in组均有不同程度的提高,其中以ICA-PGL/in组疗效最为突出(P0.01)。结论经鼻给药淫羊藿苷脂质体对帕金森病模型大鼠运动功能及神经递质的修复有不错的疗效。     

电针对帕金森病模型大鼠海马CA1区nNOS表达的影响

目的:观察不同频率电针对帕金森病(PD)模型大鼠海马CA1区神经元型一氧化氮合酶(nNOS)表达的影响。方法:将24只SD大鼠随机分为4组:正常对照组、模型组、PD模型低频电针组和高频电针组。采用右侧纹状体内注射6-羟基多巴胺(6-OHDA)制备PD模型,取合谷和太冲穴,分别给予低频(2 Hz)和高频(100 Hz)电针治疗。免疫组织化学方法观察海马CA1区nNOS表达。结果:与正常对照组相比,PD模型大鼠海马CA1区nNOS表达增加,高频电针可降低其nNOS表达,低频电针对其没有影响。结论:高频电针治疗PD的机制之一可能是通过降低PD模型大鼠海马CA1区nNOS表达。     

双相障碍躁狂发作患者背外侧前额叶皮质氢质子磁共振波谱研究

目的：研究双相障碍躁狂发作患者背外侧前额叶皮质氢质子磁共振波谱(1H magnetic resonance spectroscopy, 1H-MRS)的特点。方法：选择20例双相躁狂发作未服药患者(双相躁狂组)和20例健康志愿者(正常对照组),对其背外侧前额叶皮质行1H-MRS扫描,检测N-乙酰天门冬氨酸(NAA)、谷氨酸复合物(Glx)和肌酸(Cr)3种代谢物含量。比较两组代谢物含量,计算NAA/Cr、Glx/Cr值,并对代谢指标与病程及Bech-Rafaelsen躁狂量表(BRMS)评分的相关性进行分析。结果：双相躁狂组左侧和右侧背外侧前额叶皮质NAA/Cr值明显低于正常对照组。双相躁狂组左侧背外侧前额叶皮质Glx/Cr值明显高于正常对照组(P<0.05),而其右侧背外侧前额叶皮质Glx/Cr值与正常对照组比较,差异无统计学意义(P>0.05)。双相躁狂组背外侧前额叶皮质的代谢指标与病程及BRMS无相关性(P均>0.05)。结论：双相障碍躁狂发作患者可能存在背外侧前额叶神经生化异常。     

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Endolymphatic Hydrops

Objective: To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs. Methods: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. Results: EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVP induced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea. Conclusion: The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.     

建立类似于绝经期妇女帕金森病大鼠模型的实验研究

目的探讨利用6-羟基多巴(6-OHDA)制备模拟绝经期妇女帕金森病的大鼠模型。方法应用6-OHDA制备OVX PD模型大鼠,应用免疫组织化学染色、高效液相色谱法等技术对大鼠黑质(SN)的酪氨酸羟化酶(TH)阳性神经元数目、纹状体多巴胺(DA)及其代谢物二羟基苯乙酸(DOPAC)和高香草酸(HVA)含量进行考察并评价。结果阿朴吗啡可诱导出明显的PD大鼠旋转行为;大鼠损伤侧黑质TH阳性神经元数量较健侧显著减少(P<0.01),纹状体DA及其代谢物DOPAC和HVA含量也较健侧明显减少(P<0.01)。结论本模型具有绝经期妇女帕金森病的基本的病理特点。     

电针对血管性痴呆模型大鼠学习记忆行为及脑血红素氧化酶活性的影响

目的：探讨电针对血管性痴呆（VD）模型大鼠学习记忆行为及血红素氧化酶（HO）的影响。方法：60只大鼠随机分为假手术组、模型组、电针组和尼莫通组。用四血管阻断方法制作拟VD大鼠，造模后第10d电针组电针百会、大椎穴，1次／d；尼莫通组给予尼莫通12mg/kg稀释后，按20mL/kg灌胃，1次／d，共15d。治疗后均以水迷宫检测大鼠学习记忆行为情况，并检测皮质和海马HO活性。结果：电针组模型大鼠逃避潜伏期明显短于模型组（P＜0．01），电针组与尼莫通组之间无显著性差异（P＞0．05）；电针组在原平台象限跨越平台次数显著多于其余3个象限，而且多于模型组在原平台象限跨越平台次数。在皮质及海马，电针组和尼莫通组HO活性显著低于模型组（P＜0．01）。结论：电针能改善VD大鼠学习记忆能力，调节皮质及海马的HO活性。     

质子磁共振波谱在帕金森病大鼠模型中的应用研究

目的：探讨质子磁共振波谱（^1H-MRS）在帕金森病（PD）大鼠模型纹状体内的变化及在PD大鼠模型中的应用。方法：选用雄性Wistar大鼠12只,向其右侧纹状体内两点注射6-羟基多巴（6-OHDA）制作PD大鼠模型。5周后颈部皮下注射阿朴吗啡诱导其向健侧旋转,每分钟大于7圈者为成功模型,获6只。对照组6只大鼠以同样方法注射等剂量的生理盐水。利用BIOSPEC47／30核磁共振仪（4．7T）对双侧纹状体行^1H-磁共振波谱检测,检测后立即处死动物并行黑质及纹状体酪氨酸羟化酶（TH）免疫组织化学染色。结果：模型组大鼠右侧黑质致密部TH阳性神经元及纹状体TH阳性纤维明显减少（P〈0．01）,证明模型制作成功。模型组大鼠右侧（毁损侧）纹状体内NAA／Cr比值明显低于左侧及对照组的两侧f尸〈0．05）,对照组两侧NAA／Cr比值无显著差别。两组大鼠双侧纹状体内Cho／Cr比值均无显著差别。结论：^1H-MRS可以作为一种无创性的新技术,为偏侧大鼠PD模型纹状体部位的神经细胞的病理学改变提供有价值的信息。     

电针与锌合用对帕金森病模型大鼠一氧化氮、丙二醛等的影响

目的探讨电针与小剂量锌合用对帕金森病模型大鼠体内抗氧化酶系统的调节作用。方法选取SD大白鼠100只,将6-羟基多巴胺注入中脑右侧黑质制备单侧黑质损毁的PD大鼠模型,将模型大鼠随机分成模型组、0 Hz组和120 Hz电针组、120 Hz＋锌组和锌组,另有假手术对照组,共6组,治疗或观察6个星期,观察治疗前后PD模型大鼠行为学变化、黑质超氧化物歧化酶（SOD）、一氧化氮（NO）、丙二醛（MDA）的变化。结果与模型组比较,120Hz＋锌组大鼠损毁侧SOD、NO含量明显增加,MDA含量明显减少（P〈0.01）;在行为学方面,120 Hz＋锌组大鼠的运动平衡能力比模型组明显增强（尤其是前4周,P〈0.01）;其黑质TH阳性神经元形态学方面也有明显改善。结论电针与小剂量锌合用对帕金森病大鼠体内抗氧化酶系统具有协同调整作用,并可明显改善行为学和黑质细胞形态。     

帕金森病模型大鼠纹状体内DNA损伤与线粒体凋亡通路相关蛋白表达

目的 检测帕金森病(PD)模型大鼠纹状体内氧化DNA损伤相关指标及线粒体凋亡通路相关蛋白的表达.方法 将6-羟基多巴胺(6-OHDA)通过立体定位仪注入大鼠右侧纹状体制备PD模型,4周后观察行为学改变,5周后检测正常对照、假手术和模型组大鼠右侧纹状体内8-oxo-2'-deoxyguanosine(8-oxo-dG)免疫组化染色,Western印迹检测DNA损伤修复蛋白MTH1及线粒体凋亡通路相关蛋白Cytochrome c剪切形式的caspase 9(Cl-caspase 9)和caspase 3(Cl-caspase 3)的表达.结果 在成功筛选的10只PD模型大鼠右侧纹状体中,其8-oxo-dG阳性细胞及其吸光度A值(0.70±0.05)明显高于假手术组同侧(0.41±0.03),而MTH1蛋白表达较低,线粒体凋亡通路相关蛋白Cytochrome c,caspase 9和caspase 3表达较高,差异有统计学意义(P＜0.05).结论 由氧化应激诱导的DNA损伤在PD发病机制中起到重要作用,而线粒体凋亡蛋白参与了氧化DNA损伤诱导细胞凋亡的调控过程.     

纹状体内注射6-羟基多巴胺制作帕金森病大鼠模型

[目的]研究帕金森病(PD)大鼠模型的制作方法.[方法]采用单点双注法将6-羟基多巴胺(6-OHDA)立体定向注入到大鼠右侧纹状体,观察大鼠的行为变化和中脑黑质区的形态学变化.[结果]注药后2周,大鼠经阿扑吗啡诱导出现向健侧旋转行为,在2个月的观察中见旋转行为稳定.形态学观察结果示,损伤侧黑质区致密部和中脑被盖腹侧区内酪氨酸羟化酶阳性神经元数量明显减少.[结论]6-OHDA单针道双点法是制作大鼠PD模型的可行方法.     

纹状体注射不同剂量6-OHDA制备帕金森病小鼠模型的评价

目的纹状体内注射6-OHDA可用于制备帕金森病(Parkinson’s disease,PD)模型,其在小鼠模型上的行为学、形态学及多巴胺水平的变化需要进行系统评价。方法在小鼠右侧纹状体背外侧部立体定位分别注入4、6、8及10μg的6羟基多巴胺(6-hydroxydopamine,6-OHDA),动态观察各剂量组小鼠的基本生理状况。旋转行为和转棒行为可评价PD小鼠的运动症状;酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色可反映黑质-纹状体内多巴胺能系统的功能改变;高效液相色谱法能检测多巴胺(dopamine,DA)及其代谢产物的含量并分析DA代谢率。结果除了10μg 6-OHDA组的小鼠体质量呈一过性下降,其他剂量对小鼠体质量无显著影响。在6-OHDA注射一周后,各组小鼠均出现了持续性的异常旋转行为增加。此外,高剂量组(8μg及10μg)小鼠的转棒时间较低剂量组(4μg及6μg)小鼠明显缩短。TH组织化学染色显示,低剂量组小鼠损伤侧丢失了约60%的多巴胺神经元及40%的多巴胺神经纤维;而高剂量组小鼠则有超过80%的多巴胺神经元丢失和70%的多巴胺神经纤维减少。各组小鼠损伤侧纹状体内的DA水平及其代谢产物含量也显著降低,与6-OHDA注射量具有剂量依赖性;而DA代谢率却出现了代偿性增加改变。结论纹状体内注射不同剂量6-OHDA均能引起一定程度的PD病理表型,其损伤程度与6-OHDA剂量相关,为研究PD不同病理阶段及其干预策略提供了新的模型。     

黑质致密部和内侧前脑束注射6-OHDA 制备的帕金森病大鼠模型纹状体中 DA 含量比较

目的：：比较黑质致密部(SNc)损毁和内侧前脑束(MFB)损毁2种方法制备的帕金森病(PD)大鼠模型对纹状体中多巴胺(DA)递质含量的影响。方法：将大鼠随机分为假手术组(n=12)、SNc 损毁组(n=15)和 MFB 损毁组(n=14)。采用高效液相色谱-电化学检测法,观察3组大鼠损毁侧纹状体中 DA的含量。结果：与假手术组相比较,SNc 损毁组(P <0.001)和 MFB 损毁组(P <0.001)大鼠纹状体中 DA含量均显著降低,与 SNc 损毁组相比较,MFB 损毁组大鼠纹状体中 DA 含量下降更为显著(P =0.005)。结论：MFB 损毁制备的 PD 大鼠模型对 DA 能神经元的损伤范围较 SNc 损毁有所扩大,为不同研究选择制备模型的方法提供一定的理论依据。     

抑郁症患者脑代谢功能改变的磁共振波谱分析

目的利用磁共振波谱评价抑郁症患者是否存在认知相关脑功能区代谢物的异常改变以及MRS代谢指标同认知测试之间的相关性。方法选择我院收治的18例首次发作的抑郁症患者作为B组．10例复发的抑郁症患者做C组,另外选取12例正常志愿者A组作为研究对象,均于MR检查前接受威斯康星卡片分类测试,记录结果;之后再接受双侧前侧叶及扣带回的HRS,记录N乙酰天门冬氨酸、胆碱、肌醇、谷氨酸和谷氨酰胺复合物曲线面积的比值计算。分析二者之间的关系。结果与A组相比,C组Glx/Cr 减低,mIns／Cr升高,两组患者Glx/Cr减低,右侧前额叶mIns／Cr升高;B组、C组均存在WCST中完成总应答数、持续错误数和非持续错误数增加。B组、C组患者双侧前额叶Glx/Cr与持续错误数均呈负相关。结论抑郁症患者均存在双侧前额叶的异常代谢变化级认知功能等障碍,抑郁症患者认知障碍的病理生理学基础可能是谷氨酸能系统异常引起的。     

贝沙罗汀对帕金森大鼠黑质神经元凋亡及mTOR/AKT/GSK-3β通路的影响

目的 探讨贝沙罗汀对6-羟多巴胺诱导的帕金森大鼠黑质神经元凋亡及mTOR/AKT/GSK-3β通路的影响.方法 选取50只健康雄性SD大鼠,按随机数字表法分为假手术组,帕金森模型组,贝沙罗汀高、中、低剂量组(分别为100、50、25 mg/kg,1次/d,连续4周),每组10只.向帕金森模型组及贝沙罗汀高、中、低剂量组大鼠的右侧大脑纹状体注射6-羟多巴胺,建立帕金森大鼠模型;假手术组仅注射生理盐水.观察大鼠转圈数、速度和左前肢使用率;TUNEL染色法检测黑质神经元凋亡情况;免疫组化法检测黑质部位α-SYN的表达;Western blot检测黑质部位mTOR、p-mTOR(Ser2448)、AKT、p-AKT(Ser473)、GSK-3β和p-GSK-3β(Ser9)蛋白的表达.结果 与模型组相比,贝沙罗汀高、中、低剂量组旋转圈数、转速显著降低,左前肢使用率显著升高(P＜0.01),凋亡神经元数量显著减少(P＜0.01),黑质部位α-SYN的表达显著降低(P＜0.01),mTOR、p-mTOR、AKT、p-AKT、GSK-3β和p-GSK-3β的表达明显上调(P＜0.01).结论 贝沙罗汀对6-羟多巴胺诱导的帕金森大鼠的黑质神经元具有显著的抑制凋亡作用,其机制可能与激活mTOR/AKT/GSK-3β信号通路有关.