The Protective Effect of Rosuvastatin on Ischemic-Brain Injury and Its Mechanism

The statins, which lower plasma cholesterol levels, are 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors. To date, stains have developed to third generation, which include five commonly used stains: lovastatin, pravastatin, simvastatin, fluvastatin and atorvastatin. Recently, a new statin, named rosuvas-tatin, was used in the third stage of clinical trial. Rosu-vastatin, in contrast to most other statins, has the more powerful capability to lower plasma cholesterol levels,…     

Intrastriatal Gene Transfer of Vascular Endothelial Growth Factor Rescues Dopaminergic Neurons in a Rat Parkinson＇s Disease Model

To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson＇s disease （PD）, we constructed recombinant replication-deficent adenoviral vectors carrying the gene of VEGF165 （Ad-VEGF）, and injected Ad-VEGF （or Ad-LacZ and PBS as controls） into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase （TH） immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad-VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals, It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD.     

Intrastriatal Gene Transfer of Vascular Endothelial Growth Factor Rescues Dopaminergic Neurons in a Rat Parkinson's Disease Model

Parkinson's disease (PD) is a chronic progressivegerontic disease, which is characterized by the degeneration of dopaminergic neurons in substantia nigra. Efforhas been made to find effective treatment to arrest oslow down the degeneration of dopaminergic neuronsOnce regarded as an endothelial cell-specific factorvascular endothelial growth factor (VEGF), in recenyears, was unexpectedly found to be a critical player inneurodegeneration, and have direct neurotrophic andneuroprotective effects…     

巴曲酶治疗进展性卒中的自身对照研究

目的:观察巴曲酶在进展性卒中患者中的治疗作用.方法:对50例曾接受血液稀释治疗或中医活血化瘀类药物治疗,至少24 h未能控制症状恶化的进展性卒中患者实施标准疗程的巴曲酶治疗(10BU-5BU-5BU隔日静脉滴注),对治疗前后的神经功能缺损评分、症状停止恶化的时间以及总体疗效等给予评定.结果:于治疗开始的第1,2,3,5,7,14天分别有52%,64%,78%,90%,92%,92%患者的症状停止恶化,神经功能缺损评分也同时明显改善,治疗后的前5 d各项指标改善最明显;总有效率92%.结论:巴曲酶能迅速、有效地控制疾病的发展,减轻神经功能缺损程度,改善患者的生活能力,是现阶段治疗进展性卒中较理想的选择.     

3-硝基丙酸对沙土鼠海马CA1区锥体细胞超微结构的影响

目的　观察小剂量3-硝基丙酸(≤2 0mg/kg)对沙土鼠海马CA₁区锥体细胞超微结构的影响。方法　将沙土鼠腹腔注射不同剂量3-硝基丙酸或双蒸水后3d ,取海马CA₁区用戊二醛和锇酸固定,电镜下观察CA₁区锥体细胞层神经元细胞核和细胞器超微结构形态变化,用体视学方法计算每张照片线粒体和粗面内质网体面积变化。结果　实验组与对照组比较细胞核无明显变化,线粒体和粗面内质网轻度肿胀,体密度高于对照组。结论　小剂量3-硝基丙酸可引起神经元缺氧代偿性反应,无致死性损害。     

Rotigotine in the Treatment of Primary Restless Legs Syndrome:A Meta-analysis of Randomized Placebo-controlled Trials

The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome(RLS). Pub Med, EMBASE, and Cochrane Central Register of Controlled Trials(CENTRAL) were searched for English-language randomized controlled trials(RCTs) that assessed the effectiveness of rotigotine for RLS. The pooled mean change from baseline in International RLS(IRLS) Study Group Rating Scalescore and relative risk(RR) of response based on the Clinical Global Impression-Improvement(CGI-I) scale score were applied to evaluate the outcomes. The pooled proportions of adverse events(AEs) were also estimated. Six RCTs were included. The meta-analysis showed a favorable effectiveness of rotigotine versus placebo on RLS [mean change on IRLS score: mean difference(MD)=–4.80; 95% confidence interval(CI): –5.90 to –3.70; P<0.00001 and RR of response on CGI-I was 2.19; 95% CI: 1.86 to 2.58, P<0.00001]. The most common AEs were application site reactions, nausea, headache and fatigue. In general, rotigotine was well-tolerated in patients with primary RLS. Based on the findings from the meta-analysis, rotigotine was more significantly efficacious in the treatment of RLS than placebo. Nevertheless, long-term studies and more evidence of comparisons of rotigotine with other dopamine agonists are needed.     

凝血酶对血脑屏障通透性影响及其机制的实验研究

目的　探讨凝血酶 (TB)对血脑屏障通透性的影响及其可能机制。　方法　将TB或TB +组织蛋白酶G(CT G)立体定向注入SD大鼠右侧基底节 ,测定其血脑屏障通透性和脑水含量 ;将脑微血管内皮培养液中加入TB或TB +CT G ,相差显微镜动态观察内皮细胞形态的变化 ,免疫组织化学技术检测基质金属蛋白酶 2 (MMP 2 )表达的改变。　结果　TB脑内注射后 6h ,同侧基底节区血脑屏障通透性为 (0 4 19± 0 0 16 )A/mg (P <0 0 5 ) ,2 4h时血脑屏障通透性为 (0 5 94± 0 0 18)A/mg(P <0 0 1) ,持续至 4 8h (P <0 0 5 )逐渐消退 ,脑组织水含量的变化规律与血脑屏障通透性的变化类似。TB +CT G组在各个时间点血脑屏障通透性和脑组织水含量与对照组比较差异均无显著性 (P >0 0 5 )。TB使内皮细胞发生收缩 ,细胞收缩程度具有时间依赖性。TB入培养液 6h后 ,内皮细胞MMP 2表达水平为 (0 391± 0 0 17)A ,与对照组比较差异有显著性 (P <0 0 1)。TB +CT G加入培养液后 ,细胞形态、MMP 2表达与对照组比较差异均无显著性 (P >0 0 5 )。　结论　TB增加血脑屏障通透性是其诱发脑水肿形成的主要机制之一 ,TB通过激活蛋白酶激活受体 1(PAR 1) ,使内皮细胞发生收缩 ,促进MMP 2表达 ,是TB增加血脑屏障通透性的可能机制     

重症肌无力的免疫学发病机制研究进展

重症肌无力(MG)是抗乙酰胆碱受体抗体介导、细胞免疫依赖性、补体参与的神经肌肉接头处的自身免疫病，其发病机制是针对乙酰胆碱受体的免疫应答异常。辅助性T细胞、细胞因子及胸腺在MG的发病机制中起重要作用，肌细胞亦主动地参与了MG的发病过程。MG的免疫启动目前多倾向于交叉反应学说。     

镁对帕金森病大鼠纹状体神经肽原mRNA转录的影响

目的:研究镁对帕金森病(PD)大鼠损毁侧纹状体α-PPT、PDyn及PPE mRNA转录的影响。方法:6-OHDA损毁制备偏侧PD大鼠模型;造模成功的大鼠随机分为对照组、美多巴组、硫酸镁组和联合组,分别给予生理盐水、美多巴、硫酸镁、美多巴及硫酸镁灌胃治疗28d;RT-PCR检测损毁侧纹状体α-PPT mRNA转录水平,原位杂交法检测损毁侧纹状体PDyn、PPE mRNA转录水平。结果:美多巴组损毁侧纹状体α-PPT和PDyn mRNA转录水平较对照组增强(P0.05),硫酸镁组及联合组损毁侧纹状体α-PPT mRNA转录水平较对照组增强(P0.05),PDyn mRNA转录水平较美多巴组降低(P0.05);各组PPE mRNA转录水平无明显差异。结论:镁联合美多巴治疗PD可增加纹状体α-PPT mRNA转录水平,缓解单纯美多巴治疗导致的PDyn mRNA转录过度增强。     

格尔德霉素通过诱导热休克蛋白反应抑制DA能神经元蛋白水解应激的研究

目的探讨格尔德霉素(geldanamycin,GA)通过诱导热休克蛋白(HSP)反应抑制α-突触核蛋白(α-syn)异常表达,加强泛素蛋白酶体降解功能的神经保护作用。方法鱼藤酮作用于NGF诱导的PC12细胞建立α-syn胞质内过表达细胞模型,MTT法检测GA不同浓度及用药时程条件下的细胞活力,应用Western blot技术及共聚焦免疫荧光双标染色观察GA预处理后细胞内HSP70和α-syn的表达。荧光分光光度计测量各组细胞内蛋白酶体水解酶活性的变化。结果MTT示GA20～300nmol·L-1预处理使细胞活力呈浓度依赖性上升,吸光度分别上升至正常的65%、76%、85%和94%(鱼藤酮组为59%,P<0·01),而GA与鱼藤酮同时给药或作用于其后20h细胞活力无明显变化。Western blot结果提示GA预处理使HSP70表达上升至正常的3倍左右。共聚焦显微镜观察显示α-syn过表达现象得以抑制,并证实两者的共定位现象。酶活性测定提示GA预处理使类胰蛋白酶,类糜蛋白酶活性明显增强,荧光指数分别上升至10·4±1·61和96·0±4·77(鱼藤酮组为7·9±0·90和82·4±3·51,P<0·05),PgH水解酶活性也轻度上升。结论格尔德霉素可诱发热休克蛋白反应,主要通过HSP70的作用抑制α-syn的异常表达,促进泛素蛋白酶体降解功能,减轻蛋白水解应激反应,发挥神经保护效应。