首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 78 毫秒
1.
傅心和 《卫生职业教育》2005,23(18):124-125
阿尔茨海默病(Alzheimer'sdisease,AD)与遗传因素密切相关。研究发现,大多数早发性家族性AD(FAD)和部分散发性AD(SAD)患者存在早老素蛋白(presenilin,PS)基因突变。PS基因变异可引起β-淀粉样蛋白前体蛋白的加工和运输异常,产生过多的β-淀粉样蛋白(Aβ)而形成老年斑。对于SAD,PS表达的改变引起细胞骨架蛋白(如微管相关蛋白tau)之间的相互作用异常,而与神经纤维缠结(NFT)的形成有关。另外,PS使神经细胞对凋亡刺激的敏感性增强,以及PS基因突变产生过多的Aβ能引起脑内Bax表达增强,促进神经细胞的凋亡过程,引起AD脑内广泛的神经元减少或丢失。因此,PS在AD的发病中起到重要作用。  相似文献   

2.
载脂蛋白E与Alzheimer's病关系的研究进展   总被引:1,自引:0,他引:1  
曹方  赵瑛 《医学综述》2001,7(4):206-208
载脂蛋白是参与神经系统脂质转动和代谢的功能蛋白质,近年来发展载脂蛋白E与Alzheimer's病(AD)密切相关,研究表明,AD至少与四种基因有关,即位于19号染色体上的载脂蛋白E(ApoE)基因。21号染色体上的淀粉样蛋白前体(APP)基因,14号染色体上的早老素1(PS-1)基因及1号染色体上的早老素2(PS-2)基因,AD可分为散发性AD和家族性AD(FAD),后者根据发病年龄以又分早发型(65岁以下)和迟发型(65岁以上)。遗传学研究表明,ApoE基因的ε4等位基因是迟发型FAD的高危因子,但该基因的作用机制目前还不清楚,现就ApoE的分子结构与AD发商关系的研究进展,综述如下。  相似文献   

3.
目的观察早老蛋白-1(Presenilin-1,PS1)的过度表达对tau蛋白磷酸化的影响。方法在NC-108细胞上转染不同的PS1质粒,利用免疫双标,免疫印记,免疫细胞化学,MTT,Western blot等方法,观察早老蛋白-1的过度表达对tau蛋白磷酸化的影响。结果免疫双标显示,在散发性AD(sporadic Alzheimer disease)患者脑内,PS1主要分布于神经元,并与磷酸化tau蛋白部分共存。免疫印迹显示,与空质粒组相比,转染野生型PS1组和转染一种家族性AD(familial Alzheimer disease,FAD)突变型早老蛋白-1(mPS1)质粒组的NG-108细胞中磷酸化的tau蛋白均增加。MTT方法未检测到这两组的转染细胞与对照组有显著差异。用Confocal显微镜观察PS1-EGFP质粒转染组,发现在转染后早期12h,PS1-EGFP主要分布在细胞膜表面或细胞器上,随后PS1-EGFP主要在细胞浆中弥散分布。同时,免疫细胞化学检测显示,部分PS1-EGFP转染细胞中有明显的tau蛋白磷酸化,并且这些磷酸化tau蛋白能与PS1-EGFP蛋白一起形成聚集体。在给予磷酸酯酶抑制剂岗田酸后,PS1-EGFP转染细胞比未转染细胞含有更多的磷酸化的tau蛋白。结论野生型PS1可能参与了散发性阿茨海默氏病中的tau蛋白的病理改变。  相似文献   

4.
Alzheimer病又称老年性痴呆病(AD),它是一种涉及多因素发生学、以进行性痴呆为主要临床表现的大脑变性性疾病。在对其发病遗传因素研究中,早老素(Presemilin,PS)基因突变是近年来研究的热点。PS基因与Alzheimer病的病理进程,如与老年斑的形成有关。最新的研究认为PS基因与家族性AD和散发性AD发生均有关。  相似文献   

5.
阿尔茨海默病是一种慢性进行性神经退行性疾病,为老年痴呆最普遍的一种。目前研究认为遗传因素、环境因素和免疫因素等均参与了AD的病理生理过程。家族性AD多呈常染色体显性遗传,与淀粉样前体蛋白(APP)、早老素1(PS1)、早老素2(PS2)基因突变有关。晚发性AD(LOAD)以及散发性AD(SAD)最主要的遗传危险因子是ApoEε4等位基因,但它只与50%的AD有相关,存在其他遗传危险因子。本文就8-羟基鸟嘌呤糖苷酶1基因、环氧合酶2基因多态性与AD的关系的研究现状及进展做一简要综述。  相似文献   

6.
目的:阿尔茨海默病(Alzheimer’s disease,AD)被认为是突触相关的一类疾病,因此又把它叫做突触失效,最终导致中枢神经系统网络联系受损,认知功能及记忆能力的下降。神经元的损伤和异常信号转导是神经退行性疾病的关键性指标。因此,改善突触结构和功能障碍是改善认知缺陷和防止AD 发展的一个重要目标。文冠果壳苷是从文冠果果壳中提取的一种三萜皂苷类单体化合物,前期研究结果证实其对多种AD 模型动物的学习记忆障碍具有显著的改善作用,并可增加海马突触素及PSD95 的蛋白表达,提示文冠果壳苷可能具有保护突触或提高突触可塑性的作用。方法:本实验通过行为学、透射电镜、Golgi-Cox 染色、免疫组化、电生理和突触相关蛋白表达的考察,验证文冠果壳苷对APP/PS1 转基因小鼠学习记忆障碍的改善作用及对突触结构和功能可塑性的影响。结果:Morris 水迷宫结果表明,与APP/PS1 小鼠相比,文冠果壳苷可以显著缩短逃避潜伏期,提高穿台次数;Y 迷宫结果表明,文冠果壳苷可以显著提高APP/PS1 小鼠的自发交替反应率;提示文冠果壳苷可以改善APP/PS1 小鼠的空间记忆和工作记忆障碍。透射电镜结果表明,与APP/PS1 小鼠相比,给予文冠果壳苷后CA1 区突触间隙清晰可见,突触前区内有较多的突触小泡,突触前后膜清晰均匀;Golgi-Cox 染色结果表明,文冠果壳苷可以显著改善APP/PS1 小鼠海马树突棘密度降低;文冠果壳苷可以对抗Aβ25-35 导致的原代海马神经元树突长度降低及多级树突分枝减少;提高APP/PS1 小鼠突触结构可塑性相关蛋白(BDNF-TrkB 通路相关蛋白)的表达;提示文冠果壳苷对突触结构具有保护作用。电生理实验结果表明,文冠果壳苷可以显著改善APP/PS1 小鼠LTP 降低;CamKⅡ和GluR1 蛋白的表达对于LTP 的维持至关重要,Western blot 结果表明,文冠果壳苷可以显著提高APP/PS1 小鼠海马突触上和突触外p-CamKⅡ蛋白的表达,促进突触上GluR1蛋白的磷酸化;提示文冠果壳苷对APP/PS1 小鼠突触功能可塑性具有保护作用。结论:文冠果壳苷对APP/PS1 小鼠的学习记忆障碍具有显著改善作用。其机制可能与调节突触结构相关蛋白BDNF-TrkB 及功能维持相关蛋白CamKⅡ-GluR1,进而提高海马突触结构和功能可塑性有关。  相似文献   

7.
目的 探讨海马芳香化酶(aromatase,AROM)对APP/PS1小鼠(AD小鼠)空间学习记忆、特异性病理及突触可塑性的影响及其机制.方法 采用Western blot检测不同月龄雄性WT小鼠与AD小鼠海马AROM和雄激素受体等的表达;构建AROM的过表达病毒载体(oAROM),于6月龄AD小鼠海马立体定位注射,3个月后(9月龄)采用Morris水迷宫检测空间学习记忆行为,免疫组化/免疫荧光检测Aβ表达,Western blot检测海马Aβ和突触相关蛋白、actin细胞骨架调节蛋白表达,透射电镜检测海马突触密度、突触后膜厚度的变化.结果 WT小鼠于10月龄时海马AROM表达开始下降(P<0.01),而AD小鼠6月龄时AROM表达即显著下降(P<0.01).与APP/PS1小鼠相比,oAROM小鼠在目标象限的停留时间(P<0.05)、穿过平台次数显著增加(P<0.05),海马Aβ生成相关蛋白减少(P<0.01)而降解相关蛋白表达增加,突触密度(P<0.01)、突触后膜厚度(P<0.01)与突触蛋白表达显著增加,actin聚合蛋白Profilin-1表达显著上调(P<0.01)而解聚蛋白Cofilin显著下降(P<0.01).结论 海马特异性过表达AROM能够抑制Aβ沉积,改善痴呆小鼠海马的突触可塑性,进而改善痴呆小鼠的空间学习记忆障碍,提示海马AROM可能是预防AD的重要靶点.  相似文献   

8.
目的:探讨金钗石斛水提物(dendrobium nobile lindl,DNL)是否能通过调节突触的可塑性缓解APP/PS1阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠的学习记忆损伤。方法:12只野生型C57BL/6雄性小鼠随机分成两组(n=6):对照组(WT),单纯DNL处理组(WT+DNL):DNL(10 mg/kg,灌胃,每天1次,持续2个月);12只APP/PS1小鼠分为2组:APP/PS1 AD模型组(APP/PS1)和APP/PS1 AD模型治疗组(APP/PS1+DNL):APP/PS1小鼠7个月龄时给予DNL(10 mg/kg,灌胃,每天1次,持续2个月)。Morris水迷宫检测小鼠记忆能力;高尔基染色法检测小鼠脑海马区树突棘数量;海马脑片电生理检测长时程增强(long term potentiation,LTP);免疫组织化学技术检测海马区胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)及离子钙接头蛋白(Ionized calcium-binding adapter molecule 1,Iba1)...  相似文献   

9.
目的观察胃旁路手术对APP/PS1/Tau三转基因阿尔茨海默病模型小鼠(AD模型小鼠)认知功能的影响。方法 2018年2月—2019年3月在武汉大学人民医院中心实验室及动物实验中心进行实验,选取来自亲代APP/PS1/Tau三转基因型的子代小鼠(6月龄)随机分为AD胃旁路手术组(n=6)、AD模型组(n=6),另取相同月龄同窝生的C57小鼠随机分为WT正常对照组(n=6)、WT正常胃旁路手术组(n=6)。胃旁路手术2个月后进行APP/PS1/Tau三转基因小鼠的基因鉴定,鉴定后4组行Morris水迷宫实验检测认知功能,最后取4组小鼠海马部位组织用Western-blot方法检测P-Tau(Ser396)和P-Tau(Thr231)蛋白的表达,了解各组小鼠Tau蛋白磷酸化水平情况。结果AD模型组和AD胃旁路手术组的小鼠均携带APP、PS1及Tau 3种基因,即为APP/PS1/Tau三转基因小鼠,造模成功。在水迷宫定位航行实验中,AD胃旁路手术组小鼠较AD模型组平均逃避潜伏期明显缩短(P<0.01),而与WT正常对照组比较,AD胃旁路手术组逃避潜伏期延长(P<0.05);空间探索实验中,AD胃旁路手术组较AD模型组跨越平台次数明显增加(t=3.376,P=0.007)。AD胃旁路手术组小鼠较AD模型组Tau蛋白磷酸化水平明显降低(P<0.01)。结论胃旁路手术能明显改善阿尔茨海默病模型小鼠的认知功能。  相似文献   

10.
目的:阿尔茨海默病(Alzheimer’s disease,AD)被认为是突触相关的一类疾病,因此又把它叫做突触失效,最终导致中枢神经系统网络联系受损,认知功能及记忆能力的下降。神经元的损伤和异常信号转导是神经退行性疾病的关键性指标。因此,改善突触结构和功能障碍是改善认知缺陷和阻止阿尔茨海默病发展的一个重要目标。文冠果壳苷是从文冠果果壳中提取的一种三萜皂苷类化合物,前期研究发现其对多种AD 模型动物的学习记忆障碍具有显著的改善作用,并可增加海马突触素及PSD95 蛋白表达,提示文冠果壳苷可能具有保护突触或提高突触可塑性的作用。方法:本实验通过对行为学、透射电镜、Golgi-Cox 染色、免疫组化、电生理和突触相关蛋白表达的考察,验证文冠果壳苷对APP/PS1 转基因小鼠学习记忆障碍的改善作用及对突触结构和功能可塑性的影响。结果:Morris 水迷宫结果表明,与APP/PS1 小鼠相比,文冠果壳苷可以显著缩短逃避潜伏期,提高穿台次数;Y 迷宫结果表明,文冠果壳苷可以显著提高APP/PS1 小鼠的自发交替反应率;提示文冠果壳苷可以改善APP/PS1 小鼠的空间记忆和工作记忆障碍。透射电镜结果表明,与APP/PS1 小鼠相比,给予文冠果壳苷后CA1 区突触间隙清晰可见,突触前区内有较多的突触小泡,突触前后膜清晰均匀;Golgi-Cox 染色结果表明,文冠果壳苷可以显著改善APP/PS1 小鼠海马树突棘密度降低;文冠果壳苷可以对抗Aβ25-35 导致的原代海马神经元树突长度降低及多级树突分枝减少;提高APP/PS1 小鼠突触结构可塑性相关蛋白(BDNF-TrkB 通路相关蛋白)的表达;提示文冠果壳苷对突触结构具有保护作用。电生理实验结果表明,文冠果壳苷可以显著改善APP/PS1小鼠LTP 降低;CamKⅡ和GluR1 蛋白的表达对于LTP 的维持至关重要,Western Blot 结果表明,文冠果壳苷可以显著提高APP/PS1 小鼠海马突触上和突触外p-CamKⅡ蛋白的表达,促进突触上GluR1 蛋白的磷酸化;提示文冠果壳苷对APP/PS1 小鼠突触功能可塑性具有保护作用。结论:文冠果壳苷对APP/PS1 小鼠的学习记忆障碍具有显著改善作用。其机制可能与调节突触结构相关蛋白BDNF-TrkB 及功能维持相关蛋白CamKⅡ-GluR1,进而提高海马突触结构和功能可塑性有关。  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号