从帕金森病1817年被发现命名以来,人类与它抗争的历史已经有了二百多年.帕金森病是一种慢性进展性疾病,目前人们对该疾病认知度低、就诊率低、诊断率低.目前尚未有治愈的方法,但现有的科学治疗和疾病管理方法,已经能让帕金森病患者拥有良好的生活质量.该病虽然不影响患者的寿命,但是追求有质量的带病生活,也是所有帕金森病患者和家人的迫切需求.
Objective:To investigate the protective effect of endurance training on Parkinson disease(PD) mice and the effect of AMPK/mTOR pathway on autophagy and exosomes secretion.Methods:Thirty-two 10-week-old male C57BL/6 mice were randomly divided into quiet group, exercise group, PD quiet group and PD exercise group, with 8 mice in each group.The mice in exercise group and PD exercise group received 4-week treadmill endurance training.After training, mice in PD quiet group and PD exercise group were given rotenone (30 mg·kg -1·d -1) dissolved in 0.5% carboxymethyl cellulose salt solution and gavaged for 56 consecutive days.The mice in quiet group and exercise group were given 0.5% carboxymethyl cellulose salt solution by gavage.Then, the mice in exercise group and PD exercise group received treadmill endurance training for 4 weeks.The behaviors of mice in each group were measured after training.The content of tyrosine hydroxylase (TH) in substantia nigra of mice in each group was measured by immunohistochemistry.Western blot was used to detect the expression of plasma α-synuclein(α-syn), exosomes surface marker proteins CD9 and CD63, and the content of microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ), α-syn, adenine ribonucleotide dependent protein kinase (AMPK) and phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) in substantia nigra of mice in each group.SPSS 20.0 software was used to analyze the data.One-way ANOVA was used for comparison among multiple groups and the LSD method was used for further pairwise comparison. Results:There was significant difference in the residence time of mice in the four groups on the rotarod instrument ( F=2 618.20, P<0.01). Compared with the quiet group, the residence time of PD quiet group decreased ((110.34±8.20) s, (186.20±6.83) s, P<0.01). Compared with the PD quiet group, the residence time of PD exercise group increased ((160.56±8.30)s, P<0.01). (2) There was no significant difference in the expression of plasma exosome marker proteins CD9 and CD63 among the four groups ( F=1.57, 1.26, both P>0.05). (3) There was significant difference in the expression of α-syn in plasma exosomes of the four groups ( F=1 303.99, P<0.01). The expression of α-syn in plasma exosomes in PD quiet group was higher than that of quiet group ((180.57±8.20), (100.00±0.00), P<0.01). Compared with the PD quiet group, the expression of α-syn in plasma exosomes in PD exercise group decreased ((150.23±7.30), P<0.01). (4) There was significant difference in the number of TH positive neurons in substantia nigra among the four groups ( F=447.09, P<0.01). Compared with the quiet group, the number of TH positive neurons in the substantia nigra of PD quiet group decreased ((48.23±6.30), (100.00±0.00), P<0.01). Compared with the PD quiet group, the number of TH positive neurons in the substantia nigra of PD exercise group increased ((68.62±8.20), P<0.01). (5) Western blot showed that there were significant differences in the expression of α-syn, p-mTOR, p-AMPK and LC3-Ⅱ in substantia nigra of the four groups ( F=753.62, 361.48, 261.95, 248.07, all P<0.01). Compared with the quiet group, the expression of α-syn in substantia nigra of PD quiet group increased ((184.16±15.31), (100.00±0.00), P<0.01), the expression of p-mTOR in substantia nigra increased ((156.77±3.99), (100.00±0.00), P<0.01), the expression of p-AMPK decreased ((70.65±8.43), (100.00±0.00), P<0.01), and the expression of LC3-Ⅱ in substantia nigra decreased ((72.25±7.86), (100.00±0.00), P<0.01). Compared with PD quiet group, the expression of α-syn in substantia nigra decreased ((158.23±9.30), P<0.01), the expression of p-mTOR in substantia nigra decreased ((123.61±16.86), P<0.01), the expression of p-AMPK increased ((96.35±9.45), P<0.01), and the expression of LC3-Ⅱ in substantia nigra increased ((108.89±10.67), P<0.01). Conclusion:Endurance training regulates autophagy and the expression of exosomes in PD mice through AMPK/mTOR signal pathway, protects dopaminergic neurons in mouse midbrain and improves motor function.
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.
血管性痴呆( VD)是指由脑血管损伤引起的记忆、认知和行为等脑区低灌注的脑血管疾病所致的严重认知功能障碍综合征。我国VD的患病率为1.1%~3.0%,是仅次于阿尔茨海默病( AD)的第二常见的痴呆类型。缺血-再灌注是VD脑损伤的重要机制。ATP敏感性钾通道( KATP)的开放在保护脑缺血再灌注损伤中起着重要作用。内质网应激( ERS)在介导脑缺血再灌注导致的神经损伤中起重要作用。KATP通道通过抑制ERS反应而保护缺血再灌注的脑损伤,能阻止 VD 的发生发展。本文就ATP敏感性钾通道开放与血管性痴呆研究进展作一综述。
Objective To observe the effect of Yangxueqingnao granules on c-Fos protein expression in trigeminal nucleus caudalis (TNC) of nitroglycerin-induced migraine rats. Methods A total of 108 healthy male Wistar rats were randomly divided into normal control group, model group, high-dose treatment group, low-dose treatment group, high-dose prevention and low-dose prevention group, and then each group was randomly divided into 3 subgroups: 30, 60 and 180 min group. The experimental migraine rat model was established by subcutaneous injection of nitroglycerin. The rats of normal control group were subcutaneously injected with saline solution of the same dosage. The rats of high- and low-dose treatment group were respectively administered with gastric perfusion of high- and low-dose Yangxueqingnao granules once 10 min after the modeling. The rats of high- and low- dose prevention group were respectively administered with gastric perfusion of high- and low- dose Yangxueqingnao granules for 7 d before the modeling. The rats were sacrificed and the brain tissues were collected at corresponding time points. Related behavior indexes of rats in each group were observed and recorded. TNC c-Fos protein expression changes were measured and compared among different groups. Results At all time points, the c-Fos expression level of model group had no statistical difference from high- and low-dose treatment group ( P > 0.05, for all). However, it was higher than that in high-dose prevention group ( P = 0.031, 0.000, 0.000), while was only lower than that in low-dose prevention group at 60 and 180 min after modeling ( P = 0.000, for all). There was statistical difference between high- and low-dose prevention group only at 30 min after modeling ( P = 0.029). Conclusions The Yangxueqingnao granules can significantly decrease TNC c-Fos protein expression, which suggests that the preventive effect of Yangxueqingnao granules may be greater than the therapeutical effect on migraine. Its preventive effect may be associated with the decrease of TNC c-Fos protein expression. doi: 10.3969/j.issn.1672-6731.2014.08.012
养血清脑颗粒是以宋代中医名著<太平惠民和剂局方>的"四物汤"为基础加味,并采用最新工艺研制而成的标本兼治的制剂,是一种现代中药复方制剂,具有多靶点、多环节、整体性调节机体的特点.主要成分为当归、川芎、白芍、熟地、决明子、夏枯草、细辛等,现已成为治疗头晕、头痛、脑供血不足、高血压、眩晕、失眠等疾病的中药特效药.
<正>患者,男,58岁,主因间断头晕1年余,加重9h于2010年1月12日入院。患者间断感头晕、头闷,头重足轻感,偶觉头痛、视物模糊,但无呕吐、耳鸣、耳聋、意识障碍、肢体抽搐及活动障碍,能自行缓解,每次发作均无明显诱因,与体位改变无关。头
急性脑梗死的发病率、病死率、致残率逐年上升[1].动脉粥样硬化作为脑梗死的基础病变,不仅是脂肪浸润,同时也伴有慢性炎病损伤过程.
近年来,高同型半胱氨酸血症(hyperhomocysteinemia,Hhcy)在缺血性脑血管疾病(ischemic cerebrovascular diseases,ICVD)中的致病机制越来越受到重视,并且证实Hhcy是ICVD的一个独立危险因素 [1-4].血管性认知障碍(vascular cognitive impairment,VCI)包括所有与血管因素有关的认知改变,涵盖了血管性认知损害从轻到重的整个发病过程.本研究对40例Hhcy患者的认知功能进行了研究,探讨对认知功能的影响与颈动脉狭长的关系,为认知功能损害的早期预防和干预提供线索.
从2004年开始,我院采用银杏达莫注射液治疗急性脑梗死患者取得了明显的疗效,现报告如下.
老年脑卒中患者由于大动脉顺应性降低,常具有收缩压高、脉压大的特点.本研究探讨老年脑卒中患者脉压与心、肾损害的关系,现报告如下.
目前用于治疗急性缺血性卒中的中西药物已不在少数,但仍未能有效地减少卒中导致的致残和死亡.迅速恢复脑的灌注和减少缺血后神经元损伤是治疗缺血性卒中的两个重要策略.溶栓治疗通过迅速恢复脑血流,为治疗时间窗内就诊的患者带来功能恢复的可能[1].然而由于过短时间窗的限制,仅有少数患者受益.用于神经保护的药物还有待进一步研究和开发[2].疏血通治疗作为急性期治疗的一种方法,近来的基础与临床研究已显示它是一种有希望的治疗方法.
目的:观察碟脉灵注射液治疗脑梗死的临床疗效.方法:选择脑梗死患者100例,随机分为碟脉灵注射液组(治疗组50例)和复方丹参注射液组(对照组50例),进行临床观察.结果:治疗组总有效率90.5 %.对照组总有效率77.5 %,二组总有效率比较差异有显著性意义(P<0.05).结论:碟脉灵注射液治疗急性脑梗死有良好的疗效.
Objective To investigate the therapeutic effects of intravenous immunoglobulin (IVIG) and dynamically check the serial concentrations of IgG,IgA,IgM,CD4 +TC,CD8 +TC,and hemodynamic properties in patients with acute cerebral infarction.Methods Forty cases with acute cardiovascular disease (ACVD) were randomly divided into two groups.Group 1 patients (n=20) were treated with IVIG 2.5 g for 5 days combined with routine treatment for 15 days (as treated group,TG).Group 2 patients (n=20) only received the routine treatment as control group for 15 days (CG).Meanwhile,blood IgG,IgA,IgM,CD4 +TC,CD8 +TC,and hemodynamic indices were detected before the treatment,and 2,5,15,28 days after the treatment.Results ①The total effective rates were 90% and 60% in TG and CG respectively (P0.05). There was significant difference between the two groups.②After IVIG treatment TG had an increase in CD4 +TC,CD8 +TC,with a significant difference from CG.③After IVIG treatment TG had a decrease in IgG,with a significant difference from CG.④The two groups all got an improved conditon of blood viscosity and coagulation after treatment,but no significant difference existed between their hemodynamic indices.Conclusion Intravenous immunoglobulin used in treating acute cerebral infarction may improve the clinical curative effect,dually modulate the increased IgG level and decreased levels of CD4 +TC,CD8 +TC after cerebral infarction;but it gives no influence to the hemodynamic indices,not heightening the blood coagulation or viscosity.
随着免疫学的发展,人们逐渐认识到急性脑血管病在许多方面与免疫功能的改变有密切关系.认识免疫系统与体内大多数器官和细胞特异性接触,它的改变势必影响这些器官和组织细胞,随着年龄的增长,免疫机能减退,由此诱发出一些严重影响组织器官的疾病,加剧了机体的衰老过程和心脑血管病的发生,阻止或逆转免疫功能的衰竭,可以延缓衰老,并改变衰老免疫组织器官的严重程度[1],预防及治疗脑血管病.
目的观察不同剂量疏血通注射液治疗急性脑梗死的临床疗效.方法 90例经临床和头颅CT扫描确诊为脑梗死的患者,随机分为两组,分别给予疏血通4 ml和8 ml治疗,治疗一个疗程后根据症状及体征变化进行疗效评价,并测定血浆纤维蛋白原、D-二聚体含量,检测血流变学.结果 8 ml治疗组痊愈率、总有效率高于对照组,血浆纤维蛋白原、血液黏度降低高于对照组.结论疏血通治疗急性脑梗死疗效确切无副作用,8 ml静滴治疗临床疗效优于4 ml.
低能量氦氖激光血管内照射疗法是血液疗法的一种,目前已广泛的应用于临床.对60例急性脑梗塞患者的临床表现,血液流变学和纤维蛋白无检查结果进行分析,治疗组比对照组有效率有显著差异,血液粘度降低有显著差异,未见任何不良反应.低能量氦氖激光血管内照射疗法治疗在改善脑梗塞临床症状及降低血粘度的主要指标有较好的效果,为治疗急性脑梗塞开辟了新途径.