肌萎缩侧索硬化症(ALS)早期诊断困难,尚无有效的生物标志物以协助疾病的早期诊断、判断疾病的进展、评估预后及药物治疗反应.理想的生物标志物在患者中表达水平更高,在整个疾病过程中将保持稳定的水平,可反映疾病的治疗效果及病情的恶化,并将反映神经功能下降的速度和疾病的病程.神经丝参与神经细胞的生长、稳定和极化,促进轴突运输[1].根据其亚基的分子质量,神经丝分为神经丝轻链(NF-L)、神经丝中间链和神经丝重链.生理老化与血液和脑脊液中性神经丝水平增加有关,可能与脑脊液减少、缓慢进行的结构损害及神经丝转换的代谢改变有关[2].神经退行性疾病如ALS中亦发现高水平神经丝[3].神经丝轴突运输的下降及其随后在细胞体中的聚集改变,尤其在轴突附近细胞体中的聚集可能引起ALS中运动神经元的死亡,推测神经丝在神经变性中发挥作用.越来越多的证据表明,NF-L是轴突损伤的非特异性标志物,据报道,与其他神经退行性疾病或模拟疾病相比,ALS患者脑脊液和血液中NF-L水平更高[4].生物体液中的NF-L升高是ALS中伴随神经变性的第一个可检测到的事件.然而,它们对运动神经元病的特异性较低,在其他神经退行性疾病中水平亦增加.而血浆/血清NF-L还可被用作预后和药效学生物标志物.本综述将对NF-L在ALS中的诊断及预后的作用进行阐述.

目的 探讨白藜芦醇(resveratrol,RSV)通过调节SIRT1/AMPK信号通路对复发大鼠缺血性脑卒中的神经保护作用机制研究.方法 成年雄性Wistar大鼠38只,采用微型动脉瘤夹夹闭法制作单次大脑中动脉栓塞(middle cerebral artery occlusion,MCAO,n=14)和双次MCAO模型(n=16),随机分为RSV治疗组和实验对照组,术后3天测定各组大鼠脑梗死体积并评价行为缺损的变化.另外8只大鼠为假手术组,随机分为RSV治疗组(n=5)和对照组(n=3).采用Western blot法测定大鼠的SIRT1表达、AMPK、phospho-AMPK表达,去乙酰化荧光检测试剂盒进行SIRT1活性检测,ATP生物发光检测试剂盒测定ATP水平.结果 与对照组比较,RSV显著改善神经行为功能(P＜0.05),降低单次及双次MCAO大鼠脑梗死体积(P＜0.05),提高缺血脑组织SIRT1及AMPK活性(P＜0.05),SIRT1蛋白表达水平差异无统计学意义(P＞0.05).与对照组比较,RSV喂养3天后假手术组、单次MCAO组和双次MCAO组大鼠缺血脑组织ATP含量均显著增高(P＜0.05),RSV使组织内ATP含量升高1.5 ～2.0倍.结论 RSV对大鼠单次和双次MCAO模型均具有神经保护作用,RSV的神经保护作用与提高SIRT1及AMPK活性和增加脑缺血时能量需求有关.

Objective To evaluate the neuropsychological performance of RBD patients and its correlations with ob-jective sleep parameters. Methods Twenty-two RBD patients diagnosed by video-polysomnography( v-PSG) in neurology clinic of TianJin Medical University General Hospital and Twenty-three healthy gender,age and education-level matched subjects were enrolled. Subjects underwent neuropsychological tests,including mini-mental state examination(MMSE),Au-ditory verbal learning test(AVLT),Rey Complex Figure Test(RCFT),Clock Drawing Test(CDT),Symbol digit modalities test(SDMT),Trail Making Test A and B(TMT A and TMT B),Stroop test A,B and C,Animal fluency test(AFT),City flu-ency test(CFT),Animal-City fluency test,Boston naming test(BNT). Neuropsychological performance and objective sleep parameters were compared between the two groups,correlations between neuropsychological performance and objective sleep parameters in RBD group were analysed. Results Compared with the control group, RBD patients performed worse in MMSE,immediate memory,short and long delay recall of AVLT,time of RCFT,TMT A,TMT B,Stroop A,Stroop B,Stroop C with significant difference(P<0. 05);the mean percentage of NREM-I sleep increased,NREN-II and NREM-III sleep decreased,periodic leg movement index increased in RBD patients. Furthermore,lower sleep efficiency was correlated with decreased SDMT score(r=0. 491,P=0. 020),CFT score(r=0. 436,P=0. 043) and more time of TMT A(r= -0. 654,P=0. 001),lower total sleep time was correlated with less RCFT and BNT score(r=0. 600,P=0. 003;r =0. 482,P =0. 023),more time of TMT A(r= -0. 573,P=0. 005) in RBD patients. Conclusions RBD patients exhibited declined cognition,impaired multi-domain neuropsychological performance including vebral learning memory,exeuctive and visuospa-tial ability,disturbed objective sleep architecture,increased periodic leg movement index. Decreased total sleep time and sleep efficiency may contribute to neuropsychological performance deterioration in RBD patients.

目的 探索U0126对脑组织谷氨酸神经毒性的保护作用及可能机制.方法 健康成年雄性SD大鼠皮层注射N-甲基-D-天冬氨酸(NMDA)建立脑组织谷氨酸神经毒性模型.首先,采用不同浓度NMDA(50、100、200 mmol/L)及处理不同时间(3、6、12、24 h)筛选最佳的建模条件.根据选定的最佳条件,实验设对照组、MAPK/ERK1/2抑制剂U0126单独处理组(2 g/L)、NMDA组(200 mmol/L)、不同浓度(0.5、1、2 g/L)U0126联合NMDA处理组.各组处理24 h后处死动物,脑组织切片后行HE染色组织评价损伤;蛋白质印迹法检测损伤部位环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、Caspase-3(活化形式)及磷酸化ERK1/2(p-ERK1/2)表达水平,确定U0126在脑组织谷氨酸神经毒性损伤中的保护作用.结果 (1)NMDA以时间和浓度依赖的方式导致大鼠皮层兴奋毒性损伤,激活MAPK/ERK1/2信号通路,加重脑组织损伤,选取200 mmol/L NMDA处理24 h进行建模.(2)与对照组相比,NMDA组脑损伤部位COX-2、iNOS、Caspase-3(活化形式)、p-ERK1/2表达明显增加.U0126+NMDA处理组与NMDA组相比,COX-2、iNOS、Caspase-3(活化形式)、p-ERK1/2表达水平随U0126浓度升高而降低,脑损伤的面积显著减小.结论 U0126对大鼠皮层谷氨酸神经毒性损伤具有保护作用,其机制可能与抑制ERK1/2激活及其下游的炎症、凋亡信号途径有关.

Objective To investigate the effects of α-lipoic acid(ALA)on 6-hydroxydopamine(6-OHDA)-induced autophagy in human neuroblastoma(SH-SYSY)cells and its possible mechanisms.Methods SH-SYSY cells were divided into 5 groups:blank control group (group A),ALA group (group B),6-OHDA group(group C),ALA+6-OHDA group(group D),and rapamycin(RAPA)group (group E).The cell viability,cell apoptosis,and oxidative stress were assayed and analyzed in A-D group.The expression of autophagy-related proteins LC3-Ⅱ,AMP-activated protein kinase(AMP-K),phosphorylated AMPK (p-AMPK),the mammalian target of rapamycin (mTOR) and p-mTOR were detected by Western blot in A-E group.Results Compared with the blank control group,the 6-OHDA group significantly reduced the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜0.05),and increased the cellular apoptosis rate(P＜0.01),oxidative stress level(P ＜0.01),LC3-Ⅱ protein expression(P＜0.05,with the highest level at 6 h after treatment),and p-AMPK protein expression(P＜＜0.05).There was no significant difference in these indices between ALA group and the blank control group.Compared with 6-OHDA group,ALA+ 6-OHDA group showed that the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜ 0.05) were increased,while the cellular apoptosis rate(P＜0.01),oxidative stress level(P＜0.01),LC3-Ⅱ protein expression(P ＜0.05),and p-AMPK protein expression (P ＜ 0.05)were decreased.Conclusions The 6-OHDA can induce oxidative stress and autophagy in SH-SY5Y cells and decrease the cell viability.ALA can alleviate the 6-OHDA-induced cell injury possibly by inhibiting autophagy via AMPK/mTOR pathway.

目的 研究单发皮层下缺血性卒中的非痴呆型血管性认知障碍(VCIND)患者认知功能损害特征及在弥散张量成像(DTI)上的改变,探寻单发皮层下缺血性卒中患者发生VCIND的微结构改变特点.方法 选择单发皮层下缺血性卒中患者50例,完成认知功能评定,分为VCIND组,单纯缺血性卒中无VCIND组(SCI组),无缺血性卒中及认知功能障碍志愿者组(NC) 12例.所有符合入组标准的受试者均行核磁T1、T2成像,DTI检查、Hachinski缺血量表评分,日常生活能力指数(ADL)评分,认知功能评分及Hamilton焦虑抑郁量表评分.采集的原始图像采用统计参数图(SPM8)进行影像数据处理,分析VCIND患者在DTI像上与其他两组的微结构差异.采用基于提分析(VBA)方法对DTI图像的各项异性(FA)及平均弥散率(MD)进行统计分析.结果 VCIND组蒙特利尔认知功能评分平均(22.78士3.68)分,SCI组平均(26.87士0.82)分,NC组平均(26.11士0.33)分,差异有统计学意义(P＜0.05);VCIND组的执行功能、计算、即时记忆、注意力、语言流畅性、延迟回忆、定向力评分与SCI组比较差异有统计学意义(P＜0.05);VCIND组执行能力、延迟回忆领域得分明显低于SCI组,差异有统计学意义(P＜0.05).与SCI组比较,VCIND组FA值下降最明显区域主要在右侧前额叶眶额回内侧皮层,前扣带区域,MD增高区域在右侧眶额回;与NC组比较,VCIND组FA值下降区域主要位于双侧海马旁回,左侧前额叶皮层,左侧颞中回,右侧额下回、岛叶,左侧枕叶,右侧距状皮层,楔叶及额下回盖部;VCIND组在MD图上较NC组增高部位在左侧岛叶、额中回,脑室旁白质.结论 单发皮层下脑梗死VCIND的认知功能损害特点为多领域受损,以执行功能及延迟记忆较明显;DTI有辅助诊断筛查VCIND的影像学意义.

Objective To evaluate the sleep structure of rapid eye movement sleep disorder (RBD) patients and its correlations with emotional state,autonomic nerve system function symptoms,and sleep quality.Methods Twenty-two RBD patients examined in our hospital from October 2014 to May 2016 who complained of behavior disorders and conformed diagnosis by video-polysomnography (v-PSG) were chosen as RBD group;23 healthy gender,age and education-level matched subjects confirmed without RBD by v-PSG were selected as control group.Their emotional state,autonomic nerve function and sleep quality were assessed by center for epidemiological survey depression scale (CES-D),apathy evaluation scale (AES),scale for outcomes in PD for autonomic symptoms (SCOPA-AUT),and scale for outcomes in PD for sleep (SCOPA-SLEEP).The differences in sleep structures,periodic leg movement index (PLMI),apnea hypopnea index (AHI) and arousal index between RBD group and control group were compared.The differences of scores of emotional state,autonomic nerve system function symptoms were compared between the two groups.The correlations of sleep structure with emotional state,autonomic nerve system function symptom,and sleep quality in RBD group were analyzed.Results As compared with those of the control group,the proportion of non-rapid eye movement (NREM)-Ⅰ sleep of RBD group was significantly increased,proportions of NREM-Ⅱ sleep and NREM-Ⅲ sleep were statistically reduced,PLMI,CES-D scores,urinary and digestive system questionnaire and overall scores in the RBD group were significantly increased (P＜0.05).In patients from RBD group,CES-D scores were positively correlated with proportion of NREM-I sleep (r=0.520,P=0.000);nighttime sleepiness questionnaire and overall scores were positively correlated with PLMI (r=0.465,P=0.029;r=0.444,P=0.039);daytime sleepiness scores were negatively correlated with proportion of NREM-Ⅲ sleep (r=-0.480,P=0.041);cardiovascular system symptom was correlated with PLMI (r=0.439,P=0.041).Conclusion RBD patients suffer sleep structure disturbance,depression tendency,digestive and urinary system of autonomic nerve symptoms;sleep quality scores and total scores,cardiovascular system symptoms scores are positively correlated with LMI;daytime sleepiness is negatively correlated with reducing phase Ⅲ sleep,CES-D scores are correlated with increasing NREM-I sleep and unbalanced neurotransmitter,especially,5-TH level.

随着老龄化的加剧和脑血管疾病的增多,血管性认知功能障碍(VCI)已成为继阿尔茨海默病(AD)后导致中老年人认知障碍的第二大原因.VCI是神经系统比较常见的老年病,以进行性认知功能障碍为主要表现,其主要原因与脑内小血管病变直接相关.目前尚无特异而有效的药物进行干预治疗和阻止病程及改善患者的症状.VCI的诊断,虽然目前广泛采用头颅磁共振等技术手段,但仍然缺乏特异而针对性好的标志物来诊断,即目前仍然缺少诊断VCI的金标准.由于VCI病理类型的复杂性,部分研究转向具有良好均质性的皮质下缺血性脑血管病(SIVD).

Objective: To explore the effect of anterior circulation transient ischemic attack (TIA) on early neurological deterioration (END) in patients with ipsilateral ischemic stroke and its mechanism. Methods: (1) One hundred and thirteen patients with ipsilateral ischemic stroke and 36 healthy volunteers (healthy control group) in Neurology Department of Tianjin Medical University General Hospital from November 2014 to July 2015 were recruited into this study. According to whether got TIA before ischemic stroke, patients were divided into simple ischemic stroke group (CI group, n=87) and TIA-CI group (n=26). Their END, NIHSS score, 3-month mRS score, infarct size, serum hs-CRP and other risk factors were compared. (2) The peripheral blood mononuclear cells (PBMCs) were extracted from peripheral blood of TIA-CI group and CI group at 24 h, the 3 th day, the 7 th day and 12th day after ischemic stroke onset. At the same time, PBMCs of control group were collected. Western blot was carried out to evaluate the expression of nuclear factor-κB (NF-κB). Immunofluorescence was used to detect the cytoplasmic-to-nuclear shuttling of NF-κB. Results: (1) The incidence of END, NIHSS score at discharge, 3-month mRS score and serum hs-CRP level were significantly lower whereas the infarct size was significantly smaller of TIA-CI group than CI group (11.5% vs 31.0%, 1.9±2.3 vs 3.3±3.7, 0.9±0.8 vs 1.8±1.8, 1.1(0.3, 2.5) cm(3) vs 2.4(0.5, 22.8) cm(3,) (2.5±3.2) mg/L vs (6.2±3.2) mg/L, all P<0.05) . hs-CRP was positively correlated with END (r=0.311, P<0.05). (2) Expression of NF-κB: ① Compared with control group, the NF-κB expression increased first and then decreased in both of the two patient groups, and it decreased earlier in TIA-CI group than CI group.②In each time point, NF-κB expression of TIA-CI group was lower than CI group(t=1.754, P<0.05; t=1.858, P<0.05; t=0.609, P<0.05; t=0.519, P<0.05). (3) Activity of NF-κB: Most of NF-κB were inactivation and located in cytoplasm of control group. NF-κB of TIA-CI group and CI group was activated and translocated from cytoplasm into nuclear at the 24 h and 3 th day after ischemic stroke. At the 7 th day and 12th day, the accumulation of NF-κB in nuclear decreased and most of them located in cytoplasm in TIA-CI group, whereas most of NF-κB still located in nuclear in CI group. The activated station of NF-κB lasted shorter in TIA-CI group than CI group. Conclusions: TIA can reduce the incidence of END in patients of ipsilateral ischemic stroke. Its protective effect may relate with the inhibition of inflammation which induced by NF-κB.

Objective To establish a prediction model for 3-years recurrence after initial ischemic stroke by Cox proportional hazards regression and individual prognostic Index(PI)equation, and to evaluate its application value and external reality. Methods The inpatients with cerebral ischemic stroke hospitalized in Neurology Department in North China University of Science and Technology Affiliated Hospital were finally internalized between January 2013 and December 2013.Follow-up study on recurrence was carried out between January 2016 and December 2016.The recurrence prediction model was constructed by the Cox proportional hazards regression model.During January 2016 and December 2016,data of patients with ischemic stroke were prospectively continuously collected.And PI equation was used to verify its external reality in ischemic stroke patients. Results A total of 184 cases had stroke recurrence during the follow-up period.The Cox proportional hazards regression model analysis showed that age(RR=1.303,95% CI:1.019-1.666),history of heart disease(RR=1.788,95% CI:1.127-2.836),hypertension(RR=1.897,95% CI:1.097-3.280),diabetes(RR= 1.674,95% CI:1.015-2.760)and total cholesterol(RR= 2.136,95% CI:1.396-3.266)were the independent risk factors for stroke recurrence.The established recurrence model was correlated with individual PI equation,which was PI = 0.265X1+ 0.581X2+ 0.640X3+ 0.515X4+0.759X5.By the validation study of PI equation to predict stroke recurrence among patients admitted later, the sensitivity was 0.719,specificity was 0.769,and accuracy was 0.800. Conclusions Age,history of heart disease,hypertension,diabetes,and total cholesterol are independent risk factors for recurrence of ischemic stroke.And the PI for predicting stroke recurrence within 3 years after initial stroke is successfully established,which is good and helpful for predicting ischemic stroke recurrence.

原发性进行性失语(primary progressive aphasia,PPA)是一组以特定语言功能进行性丧失,而其他认知功能相对保留为特点的综合征.2010年提出的分类方法将PPA分为3种亚型:非流利型/语法缺失型、语义变异型和寡语型.其中寡语型PPA(logopenic primary progressive aphasia,LPA),也称为“LV-PPA”或“PPA-L”,是由Mesulam在1982年最早描述的,其核心特征为词语提取障碍和语句复述能力受损.目前,越来越多的研究关注LPA患者语言损害及机制,本综述将对LPA语言损害特点及其形成机制的最新研究进展进行讨论,希望能增进人们对LPA的认识和研究.

Objective To establish Cox proportional hazards regression model and individual prognosis index (PI) equation for the 3-year recurrence of ischemic stroke and to verify their external reality according to their propective application.Methods A total of 1058 first-ever ischemic stroke patients admitted to our hospital were followed up from 2013-01-01 to 2013-12-31,during which the recurrence of ischemic stroke was recorded.Cox proportional hazards regression model and PI equation for the 3-year recurrence of ischemic stroke were established.Six hundred and sixteen first-ever ischemic stroke patients admitted to our hospital were followed up from 2016-01-01 to 2016-12-31.The external reality of Cox proportional hazards regression model for the 3-year recurrence of ischemic stroke was verified according to the established PI equation.Results Of the patients who were followed up in 2013,ischemic stroke reoccurred in 184.Cox proportional hazards regression model analysis showed that age,heart disease,hypertension,diabetes mellitus and TC were the independent risk factors for the recurrence of ischemic stroke.Of the patients who were followed up in 2016,ischemic stroke reoccurred in 114.The sensitivity,specificity and accuracy of PI equation in predicting the recurrence of ischemic stroke were 71.9％,76.9％ and 80.0％ respectively.Conclusion Establishment of PI equation for the 3-year recurrence of ischemic stroke can predict the recurrence of ischemic stroke.

Objective To investigate the risk factors and establish the Cox's regression model and the personal prognosis index for the recurrence of ischemic stroke in 3-year follow-up.methods 1058 patients were retrospectively reviewed consecutively diagnosed with ischemic stroke admitted to the Neurology Department of the Hebei united University Affiliated Hospital from January 1,2013 to December 31,2013.Cases were followed up since the onset of ischemic stroke.The follow-up was finished in January 1,2016.Kaplan-Meier methods were used for recurrence rate description.Monovariant and multivariate Cox's proportional hazard regression model were used to analyze risk factors associated with recurrence.Thus,a recurrence model was set up.Result sDuring the period of follow-up,184 cases relapsed.The 1-year recurrence rate was 29.9 person-year,2-year recurrence rate was 46.6 person-year,3-year recurrence rate was 52.7 person-year.Monovariant and multivariant Cox's proportional hazard regression model showed that the independent risk factors associated with recurrence were age(X1)(RR=1.303;95%CI:1.019~1.666)history of heart disease(X2)(RR=1.788;95%CI:1.127~2.836),hypertension(X3)(RR=1.897;95%CI:1.097~3.280),diabetes(X4)(RR=1.674;95%CI:1.015~2.760),total cholesterol(X5)(RR=2.136;95%CI:1.396~3.266).The personal prognosis index(PI)of recurrence model was as the following: PI=0.265X1+0.581X2+0.640X3+0.515X4+0.759X5.Conclusion sAge,history of heart disease,hypertension,disease progression,and total cholesterol are the independent risk factors associated with recurrence of ischemic stroke.The recurrence model and the personal prognosis index equation are successful constructed.

Objective To study the effects of lipoic acid on cognitive function and oxidative stress in rats with impaired glucose regulation.Methods Male Wistar rats were randomly divided into 5 groups:control group,model group,lipoic acid low 15 mg/(kg/d),medium 30 mg/(kg/d),high 60 mg/(kg/d) dose group.A rat model of impaired glucose regulation was established by feeding with high fat and high sugar diet.The model rats were fed with lipoic acid solution 15,30 and 60 mg/kg daily,1 times daily,with a total of 14 d.The learning and memory abilities of rats were measured by Morris water maze method,and the content of ROS in hippocampus of rats in each group was detected by flow cytometry.Results Compared with the control group,the learning and memory ability of the model group decreased (P<0.05),while the level of ROS in the hippocampus increased (P<0.05).Compared with the model group,the level of ROS in the brain decreased in the lipoic acid group,and the learning and memory ability of the rats increased,especially in the middle dose group (P<0.05).Conclusion Lipoic acid has protective effects on cognitive function in rats with impaired glucose regulation,and its protective effects are related to its antioxidant effects.

Objective To study the inhibitory effect of panax notoginseng saponins (PNS) on 3-nitrotyrosine (3-NT) formation in brain induced by heme/NO2 -/H2O2 or ONOO - pathways in vitro. Methods According to the two major pathways of 3-NT formation in vivo, the models of protein nitration induced by heme/NaNO2/H2O2 or ONOO-system were established, respectively, in vitro. Bovine serum albumin (BSA)/rat plasma protein or rat brain homogenate protein were utilized as reactive substrates in both systems. Samples were divided into blank-control group, 3-NT group and PNS group (including low-, medium-and high-concentration subgroups). In 3-NT group, samples were exposed to heme/NaNO2/H2O2 or ONOO-system, respectively, at 37℃for 30 min, whereas in PNS group, samples were pre-incubated with PNS (at final concentrations of 50 mg/L, 100 mg/L, and 200 mg/L) at 37℃for 5 min before the nitrating system exposure. The 3-NT level in each group was detected by Western blot assy. Results Compared with the blank-control group, both heme/NaNO2/H2O2 and ONOO-system can induce significant 3-NT generation in BSA/rat plasma protein or rat brain homogenate protein (P<0.05). Compared with model group, PNS pre-treatment markedly inhibited 3-NT expression in BSA/rat plasma protein in a dose-dependent manner (P<0.05), the inhibitory effect of low intervention on the level of 3-NT in rat brain homogenate protein was not significant (P>0.05). Medium- and high-concentrations of PNS pre-treatment markedly inhibited 3-NT accumulation, with maximum effect at the concentration of 200 mg/L (P<0.05). Conclusion Medium- and high-concentrations of PNS can inhibit 3-NT formation in brain tissue mediated by either heme/NO2-/H2O2 or ONOO-pathways, implying that potential neuroprotective action against 3-NT involves pathological conditions, like trauma, stroke, and neurodegenerative diseases.

Objective To observe the expression changes of 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) in brain tissues of ischemia-reperfusion rats treated with different doses of hydroxysafflor yellow A (HSYA) by intravenous injection.Methods The healthy adult male SD rats were randomly divided into the sham operation group, model group, low-dose HSYA group, medium-dose HSYA group and high-dose HSYA group.In the sham operation group, rats' common carotid artery, internal carotid artery and external carotid artery were exposed, and then sutured.The other rats were subjected to a 60-min middle cerebral artery occlusion and 24-h reperfusion (MCAO/R).The rats in the low-dose, medium-dose and high-dose HSYA groups were injected with 2.5, 5 and 10 mg/kg HSYA, respectively, in the tail vein at 60 min after ischemia, and the same volume of Tris buffer was injected into the tail vein of rats in sham operation group and model group.All rats were continued to raise for 24 h.The expression of 3-NT and iNOS in the rat brain tissues after ischemia-reperfusion in each group was examined by Western blotting.The NO level was also detected by Griess assay.Results The absolute gray values of 3-NT in the sham operation group, the model group, the low-dose HSYA group, the medium-dose HSYA group and the high-dose HSYA group after ischemia-reperfusion were (2.81±1.37)×103, (46.86±4.75)×103, (44.51±4.13)×103, (13.88±2.98)×103, and (6.38±2.66)×103, respectively;the absolute gray values of iNOS of each group were (2.25±0.32)×103, (79.67±4.73)×103, (75.29±4.08)×103, (27.31±2.77)×103, (19.19±1.86)×103, respectively.In the model group and low-dose, medium-dose, and high-dose HSYA groups, the levels of NO were (16.50±2.20), (15.40±1.44), (10.33±1.30), and (6.80±0.73) nmol/mg.The levels of 3-NT, iNOS and NO in brain tissues of the model group, low-dose HSYA group, medium-dose HSYA group and high-dose HSYA group were higher than those of the sham operation group (all P<0.05).The levels of 3-NT, iNOS and NO in the brain tissues of rats in the low-dose HSYA group were not significantly different from those in the model group (P>0.05).The levels of 3-NT, iNOS, NO in the medium-dose and high-dose HSYA groups were lower than those in the model group and low-dose HSYA group (all P<0.05), and the levels of 3-NT, iNOS and NO in brain tissues of high-dose HSYA group were lower than those in medium-dose HSYA group (all P<0.05).Conclusion HSYA can inhibit the expression of 3-NT, iNOS, and NO in rat brain tissues after ischemia-reperfusion.The higher the HSYA dose is, the more obvious the effect will be.

Objective To study the effects of Hydroxysafflor yellow A(HSYA)on brain protein carbonylation induced by peroxynitrite(ONOO-)and heme/NaNO2/H2O2 system in vitro.Methods To simulate in vivo peroxynitrite(ONOO-)and heme/NaNO2/H2O2 system-induced carbonylative pathway,with brain protein for nitrification substrates,divided into blank group,control group and HSYA intervention groups(doses of 0.1 and 1 mM,respectively).2,4-dinitrophenylhydrazine(DNPH)was used for the quantification of protein carbonylation.Results The treatment of brain tissue with ONOO-or heme/NaNO2/H2O2 resulted in the significant formation of carbonyl groups.HSYA,at doses of 0.1 and 1 mM,dose-dependently decreased ONOO-induced protein carbonylation by 26.13% and 46.23% respectively,the difference was statistically significant(F=14.625,P<0.05).However,HSYA was relatively ineffective in protecting brain tissue from heme/NaNO2/H2O2-induced oxidative damage,the difference was not statistically significant(P>0.05).Conclusion HSYA could dose-dependently inhibit brain protein carbonylative modification induced by ONOO-system in vitro,which may be one of the molecular mechanisms to against cerebrovascular and neurodegenerative diseases.

Objective To study the effect of dimethyl fumarate (DMF) on Aβ-induced oxidative stress by regulating NF-E2-related factor 2 (Nrf2) expression and its mechanism.Methods Rat astrocytes were divided into Aβ group,DMF group,Nrf2 group and Nrf2 +DMF group.Expressions of Nrf2,Nqo1,Ho-1,Keap1 mRNA and HDAC were detected by RT-PCR and Western blot respectively.Results The expression levels of Nrf2,Nqo1 and HO-1 mRNA were significantly lower in Nrf2 group and Nrf2+DMF group than in Aβ group and DMF group (P＜0.05) and were significantly higher in DMF group than in Aβ group (P＜0.05) while the expression level of Keap1 mRNA was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (P＜0.05).The expression level of HDAC was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (6.41±0.43 vs 9.01±1.54,P＜0.05;6.72±0.30 vs 8.76± 0.74,P＜0.05).Conclusion DMF increases the Nrf2 expression by inhibiting the HDAC expression,thus reducing Aβ-induced oxidative stress in rat astrocytes.

目的 观察社区脑卒中及其高危人群失眠与阻塞性睡眠呼吸暂停(OSA)高风险的发生率并对其影响因素进行分析.方法 2015年2月对天津市大张庄村和劝业场社区3500例本市户籍常住居民进行横断面调查,选择脑卒中及其高危人群信息完整者作为研究对象,根据阿森斯失眠量表测评标准将研究对象分为失眠组241例和无失眠组380例.采用Stop-Bang量表测评将研究对象又分为OSA高风险组410例和OSA低风险组211例.结果 筛查结果显示,失眠组焦虑自评量表(SAS)评分[(37.40±9.14)分 vs (29.38±4.45)分,P=0.000]、抑郁自评量表(SDS)评分[38.32±10.95)分 vs (30.07±6.18)分,P=0.000]显著高于无失眠组.社区脑卒中及其高危人群失眠发生率为38.8％,OSA高风险率为66.0％.logistic分析短暂性脑缺血发作、饮酒,SDS评分、SAS评分是影响失眠的独立危险因素;男性、体质量指数、颈围、高血压、心脏病是影响OSA高风险的独立危险因素(P＜0.05,P＜0.01).结论 社区脑卒中及其高危人群中,短暂性脑缺血发作、饮酒及焦虑抑郁状态对失眠的发生产生显著影响,而男性、肥胖、颈围、高血压及心脏病与OSA高风险相关,对社区脑卒中及其高危人群早期进行上述因素的筛查,有助于脑卒中一、二级预防.

Peroxisome proliferators-activated receptor γ (PPARγ) belongs to a nuclear receptor superfamily. Many studies have shown that PPARγ can help to improve the outcome of cerebrovascular disease. PPARγ can reduce inflammatory response, oxidative stress as wel as enhance the hematoma removal abilities of microglia and macrophages, and it plays an important protective role in intracerebral hemorrhage.