葛根素对去卵巢大鼠机体骨代谢影响的观察

目的 观察葛根素对去卵巢大鼠机体骨代谢的影响,探讨其对雌激素缺乏引起的骨质疏松症的治疗作用.方法 3月龄清洁级SD大鼠60只,背驮式切除双侧卵巢后每日灌胃葛根素5 mg/kg(P-5组),10 mg/kg(P-10组)和20 mg/kg(P-20组),并设假手术组(Sham),模型组(OVX)和己烯雌酚阳性对照组(E).3个月后处死动物,测定大鼠胫骨干重、灰分重量和矿物质含量,胫骨Ca、P含量以及血清相关骨代谢指标.结果 与OVX组相比,葛根素各组的胫骨矿物质含量(mg/g)均有增加(574±17,590±22和597±18),其中P-20组差异显著(P＜0.05);葛根素各组的胫骨Ca含量(mg/g)高于OVX组 (132±10,222±7,228±8),其中P-10,P-20两组差异显著(P＜0.05,P＜0.01),说明服用葛根素后大鼠骨量得到增加;同时,葛根素各组的碱性磷酸酶(U/L)与OVX组有所降低(101±26,90±20,71±15),其中P-10,P-20两组差异显著(P＜0.05,P＜0.01),说明去卵巢大鼠骨的高转换状态得到改善.结论 葛根素能抑制去卵巢大鼠骨量的丢失,对骨代谢有较好的调节作用,对雌激素缺乏引起的骨质疏松症有一定的治疗作用.     

葛根素联合雌二醇对去卵巢大鼠骨质疏松的治疗作用

目的了解小剂量葛根素联合雌二醇对去卵巢大鼠骨质疏松(OP)治疗作用,为中西医结合治疗Ⅰ型OP提供实验依据。方法 5月龄健康雌性大白鼠120只,分成5个实验组(n=24):①假手术组(sham);②去卵巢模型组(OVX);③葛根素组(Pr),皮下注射葛根素,50 mg/kg,1次/d;④雌二醇组(E2),皮下注射雌二醇200μg/kg,2次/w;⑤小剂量葛根素+雌二醇组(Pr+E2),皮下注射雌二醇100μg/kg,2次/w和葛根素25 mg/kg,1次/d。各实验组在第4、8、12和20周,随机取6只大鼠处死,取左股骨切片观察骨组织,取右股骨测量骨密度(BMD),取左心血测量血清雌二醇(E2)、碱性磷酸酶(AKP)。结果 OVX组的血清E2和BMD明显低于sham组(P<0.01),而血清AKP明显高于sham组(P<0.01);3个治疗组各时间的血清E2、AKP和BMD无显著差异(P>0.05)。小剂量的葛根素联合雌二醇治疗能使去卵巢大鼠骨组织、血清E2、AKP和BMD接近正常(P>0.05),与较大剂量的葛根素组或较大剂量的E2组相比无明显差异(P>0.05)。结论小剂量的E2与葛根素对去卵巢大鼠的治疗效果与单独使用较大剂量的葛根素或较大剂量的E2相比治疗效果相近。     

山茶籽与葛根素对去卵巢大鼠骨质疏松的防治作用比较

目的探讨山茶籽与葛根素对去卵巢大鼠的骨组织形态结构、骨密度和碱性磷酸酶的影响。方法5月龄雌性大鼠32只,分成4个试验组(每组8只):(1)假手术(Sham)组;(2)去卵巢模型(OVX)组;(3)山茶籽治疗(Ts)组:山茶籽醇提物灌胃,10 ml/kg,1次/d(5 g/g生药);(4)葛根素治疗(Pr)组:皮下注射葛根素,50 mg/kg,1次/d。各试验组在4、12 w,麻醉大鼠采血测定碱性磷酸酶,12 w后处死右侧股骨切片染色镜观骨组织结构,右侧股骨烘干测量骨密度,数据常规计算分析。结果与Sham组比较,OVX组骨组织镜下观骨质疏松明显,血碱性磷酸酶升高明显(P<0.01)。Ts组、Pr组、Sham组骨切片组织结构、骨密度和碱性磷酸酶差异无统计学意义(P>0.05)。结论山茶籽和葛根素对去卵巢大鼠的骨质疏松有防治作用,疗效相近。     

葛根素对去卵巢大鼠认知功能及海马神经元超微结构的影响

目的 观察不同浓度葛根素对去卵巢大鼠认知功能及海马CA1区、CA3区神经元电镜下形态的影响.方法 SD大鼠72只,随机分为葛根素高、中、低剂量组、阳性对照组(倍美力组)、模型组、假手术组,每组12只,除假手术组外,均摘除大鼠卵巢造成去势模型.灌胃30 d后,用Morris水迷宫检测大鼠认知功能的变化,用透射电镜观察海马CA1区、CA3区神经元形态变化.结果 在训练第6天,Morris水迷宫试验测试大鼠第一次经过平台的时间(潜伏期)与模型组比较,假手术组、阳性对照组和葛根素高剂量组有统计学意义(P＜0.05);大鼠在120 s内经过平台的次数与模型组比较,假手术组、阳性对照组和葛根素高剂量组有统计学意义(P＜0.01);与低剂量组比较,葛根素高剂量组有统计学意义(P＜0.05).透射电镜结果表明,葛根素在不同浓度(30～ 120 mg/kg)范围内,随着浓度的增大,抑制海马神经元细胞凋亡的作用越强,并有一定的剂量依赖关系.结论 葛根素可以促进去卵巢大鼠学习、记忆功能的恢复,减轻因雌激素缺乏而引起的大鼠海马神经元凋亡作用.     

葛根素对去卵巢大鼠骨质疏松和血脂的作用

激素替代疗法（HRT）对绝经后骨质疏松防治效果肯定，但HRT使心血管疾病发生的相对风险增加22％，对脂代谢影响尚无定论，长期应用可引起子宫内膜癌和乳腺癌。一些植物雌激素具有选择性雌激素受体调节功能，与合成雌激素有相似的抗绝经后骨质疏松作用。葛根素属植物雌激素，有扩张血管、改善心脑供血和抗动脉粥样硬化的作用。近年的研究表明，葛根异黄酮可降低去卵巢大鼠肝内胆固醇（TC）和甘油三酯（TG）水平，体外研究提示葛根素有抑制骨吸收的作用，但葛根素对去卵巢大鼠骨质疏松和血脂代谢的系统研究报道较少。我们对去卵巢大鼠模型给予葛根素，观察骨质疏松大鼠骨密度、骨生物力学指标和血脂的变化。     

葛根素对去卵巢大鼠体重及大脑海马CA1区、CA3区神经元形态的影响

目的 观察不同浓度葛根素对去卵巢大鼠体重及海马CA1区、CA3区神经元形态的影响.方法 SD大鼠72只,摘除卵巢1 w后,随机分为葛根素高、中、低剂量组、倍美力组、模型组、假手术组,每组12只,除假手术组外,均摘除大鼠卵巢造成去势模型.灌胃过程中每5天称重一次,30 d后,用HE染色观察海马神经元形态变化.结果 与模型组比较,葛根素在不同浓度(30～ 120 mg/kg)范围内,随着浓度的增大,抑制海马神经元细胞凋亡的作用越强,并有一定的剂量依赖关系;但对大鼠体重变化无明显影响.结论 葛根素可以抑制大鼠海马神经元细胞的凋亡,而对大鼠体重改变无显著作用.     

去卵巢、去松果体对大鼠齿状回突触泡膜素表达的影响

衰老及阿尔茨海默病 (Alzheimer' s,AD)多发于老年 ,主要为记忆障碍 ;受损脑区主要为联合皮质区、海马结构等 ;突触丢失是衰老尤其 AD病理特征之一。研究显示突触丢失在记忆障碍中起重要的作用[1 ] ,然而突触丢失的原因及机制至今不是很清楚。老年期雌激素 (E)、褪黑素 (MT)水平同时大幅下调 ,有些实验显示 E、 MT水平能影响突触的可塑性 [2～ 3] ,但是 E、MT单独及联合缺乏影响突触的可塑性的能力比较至今未见研究报道。突触泡膜素(SYN)是突触前膜上的特异性蛋白 ,可用来反应突触的可塑性。因为 E、MT分别主要在卵巢、松果体产生 ,…     

葛根素对绝经后骨质疏松大鼠血清OPG、RANKL和骨组织的影响

目的探讨葛根素对绝经后骨质疏松大鼠的护骨素、核因子-κB受体活化因子配体、碱性磷酸酶和骨组织的影响。方法 5月龄健康SD雌性大鼠96只,随机分为:假去卵巢(Sham)组;绝经后骨质疏松模型(OVX)组、山茶籽治疗(Ts)组、雌二醇(E2)治疗(E2)组。比较各组第2、6、8和12 w,护骨素、核因子-κB受体活化因子配体和碱性磷酸酶水平,观察各组股骨头组织结构。结果 OVX组股骨头组织有明显疏松病理改变,护骨素明显低于Sham组、Ts组和E2组。OVX组核因子-κB受体活化因子配体、血清碱性磷酸酶明显高于Sham组、Ts组和E2组。结论葛根素有雌激素样作用对绝经后骨质疏松有防治作用。     

黄连素对阿尔茨海默病模型大鼠的保护作用

目的探讨黄连素(BC)对阿尔茨海默病(AD)模型大鼠空间学习、记忆能力的影响并探讨其作用机制。方法采用尾静脉注射同型半胱氨酸建立AD模型,术后给予BC治疗。Morris水迷宫实验检测大鼠的空间学习、记忆能力;采用过氧化氢酶(CAT)、谷胱苷肽过氧化物酶(GSH-Px)检测试剂盒检测CAT、GSH-Px活性;Western印迹法检测凋亡信号通路蛋白表达。结果经黄连素治疗后,AD模型大鼠的学习、记忆能力有显著改善(P0.05)。经黄连素治疗后,AD模型大鼠的海马组织中CAT、GSH-Px活性显著升高(P0.05)。黄连素逆转AD模型大鼠凋亡通路相关蛋白水平(P0.05)。结论黄连素能改善AD模型大鼠的空间学习、记忆能力;促进自由基清除和抗凋亡可能是其作用机制。     

密骨胶囊对去卵巢大鼠骨质疏松模型的影响

目的 探讨密骨胶囊对去卵巢骨质疏松模型大鼠腰椎整体骨量和骨质成分丢失的影响。方法 40只10月龄Wistar雌性大鼠随机分为正常组、模型组、密骨胶囊组和倍美力组,每组10只。正常组仅行假手术,其余三组行卵巢切除术。术后91天开始给药,连续用药满90天,处死,取出第2腰椎,测定整体骨量和钙、磷、有机质含量。结果 密骨胶囊能明显提高骨质疏松大鼠腰椎骨的整体骨量和钙、磷、有机质含量。结论 密骨胶囊能增强骨质疏松大鼠腰椎的骨量,改善骨结构。     

维生素E对Alzheimer病模型大鼠的影响

采用ＡｌＣｌ３诱导，建立Ａｌｚｈｅｉｍｅｒ病（ＡＤ）模型大鼠。用维生素Ｅ（ＶＥ）（５ｍｇ／１００ｇ体重·ｄ－１）对ＡＤ模型大鼠进行灌胃治疗。通过行为测试，光镜形态学观察，用免疫细胞化学ＡＢＣ结合图像定量分析的方法，对ＡＤ大鼠行为改变，海马结构ＣＡ１区淀粉样蛋白免疫反应阳性神经元的形态和数目、胞体平均截面积和光密度以及β淀粉样蛋白的沉积变化进行观察。结果显示ＶＥ组大鼠治疗３个月和５个月后，受电击次数和潜伏期较对照组明显减少和延长（Ｐ＜００１），３个月与５个月之间有显著性差异（Ｐ＜００１）；ＶＥ组大鼠海马结构ＣＡ１区淀粉样蛋白免疫反应阳性神经元的形态和数目、胞体平均截面积和光密度值，３个月和５个月较对照组均有明显减少和降低（Ｐ＜００１），３个月和５个月之间也有显著性差异（Ｐ＜００１），β淀粉样蛋白样反应染色减少或消失。说明ＶＥ可以改善ＡＤ模型大鼠的学习记忆，其作用机制是通过抑制和清除海马结构ＣＡ１区β淀粉样蛋白的沉积来实现的，作用效果随治疗时间的延长而更加明显。本实验研究结果为临床应用ＶＥ治疗老年性痴呆提供了形态学依据。     

�����ĺ�Ĭ�������о��������н�չ

阿尔茨海默病是最常见的老年认知障碍,本文着重对阿尔茨海默病的治疗研究领域中的热点进行点评,包括Aβ聚集抑制剂、Aβ生成抑制剂、Aβ介导的神经递质抑制剂、Tau介导的神经毒性抑制剂等。对在困境中的AD治疗研究如何进一步深入,提出需要重新审视的问题。     

Thiamine therapy in Alzheimer's disease

Fursultiamine (TTFD), a derivative of thiamine, at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer's disease in a 12-week open trial. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. Alzheimer patients' blood levels of thiamine before the trial were within the normal range. No adverse reactions were observed and all patients tolerated the trial well. TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients. However, further investigations of the therapeutic implications of thiamine and its possible etiologic clues to Alzheimer's disease are necessary.     

Screening for Alzheimer's disease: the memory impairment screen versus the conventional three-word memory test

OBJECTIVES: To improve screening for Alzheimer's disease (AD) with the Memory Impairment Screen (MIS), a 4-minute, four-item delayed free and cued recall memory test with controlled learning and high discriminative validity. To assess the discriminative validity of the MIS for AD and to compare it with the conventional three-word memory test, a delayed free recall task, widely recommended as a dementia-screening test in clinical practice. DESIGN: Cross-sectional validation study nested within a longitudinal study of aging and dementia. The MIS and the standard three-word memory task were administered as part of a comprehensive neurological and neuropsychological evaluation. SETTING: Einstein Aging Study at the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: Two hundred forty community-dwelling older adults. MEASUREMENTS: Sensitivity, specificity, and positive predictive value (PPV) were calculated for the MIS and three-word memory test as screening tests for AD. RESULTS: In comparison with the three-word memory task, the MIS had higher sensitivity (.86 vs.65), higher specificity (.97 vs.85), and greater PPV (.80 vs.37) as a screen for AD. CONCLUSIONS: The MIS had high discriminative validity as a screening test for AD and substantially outperformed the three-word memory task. Given its validity and brevity, the MIS has important advantages as an AD screen for use in primary care.     

Apathy in Alzheimer's disease

Apathy, or loss of motivation, is arguably the most common change in behavior in Alzheimer's disease (AD) but is underrecognized. Apathy represents a form of executive cognitive dysfunction. Patients with apathy suffer from decreased daily function and specific cognitive deficits and rely on families to provide more care, which results in increased stress for families. Apathy is one of the primary syndromes associated with frontal and subcortical pathology, and apathy in AD appears to have multiple neuroanatomical correlates that implicate components of frontal subcortical networks. Despite the profound effects of this common syndrome, only a few instruments have been designed to specifically assess apathy, and these instruments have not been directly compared. Assessment of apathy in AD requires clinicians to distinguish loss of motivation from loss of ability due to cognitive decline. Although apathy may be misdiagnosed as depression because of an overlap in symptoms, current research has shown apathy to be a discrete syndrome. Distinguishing apathy from depression has important treatment implications, because these disorders respond to different interventions. Further research is required to clarify the specific neuroanatomical and neuropsychological correlates of apathy and to determine how correct diagnosis and treatment of apathy may improve patient functioning and ease caregiver burden.     

Impediments to timely diagnosis of Alzheimer's disease in African Americans

The purpose of this study was to identify early patterns of care for Alzheimer's disease (AD) in a cohort of African-American patients and their caregivers presenting at an inner city clinic and a suburban memory assessment clinic. Caregivers (N=79) of patients diagnosed with probable AD were interviewed. Data were collected about the delay from noticing first AD signs until recognition that a problem existed and delay from problem recognition until first physician consultation. Patients and caregivers had lower educational status, and patients had been diagnosed more recently at the inner city clinic than at the suburban clinic, although MMSE scores of patients at the two clinics did not differ; median delays in caregivers' recognizing a problem and in consulting a physician were also similar across clinics. Delay was as long as 7 years between noticing symptoms and problem recognition and between problem recognition and physician consultation. Although patients attending the suburban clinic were more likely to have previously seen a physician than those attending the inner city clinic, they were no more likely to have received a prior diagnosis of AD. Lack of physician contact is likely to be widespread in families caring for African Americans with AD. Physician consultation is more characteristic of more highly educated families but may not yield a correct diagnosis for the patient. Intensive efforts are needed to connect African-American families with physicians and to achieve more timely diagnosis of AD to enable families to understand the illness, plan for patient safety, and make long-term plans.     

The impact of symptom severity on the cost of Alzheimer's disease

OBJECTIVES: ITo examine the economic impact of Alzheimer's disease (AD) as the disease progresses on patients' medical costs and caregivers' productivity. DESIGN: A 12-page, self-administered mail survey, fielded in November 1999. SETTING: Households with AD caregivers, selected from a nationwide (U.S.) consumer database. PARTICIPANTS: One thousand seven hundred fifteen caregivers of noninstitutionalized AD patients. MEASUREMENTS: Disease progression was measured using a scale of symptom frequency and measures of instrumental and physical functioning. Cost components included hospital days, physician visits, and emergency room visits. Lost productivity was assessed using hours per week that caregivers provided care and the number of days that they missed from work because of caregiving. RESULTS: The direct costs of caring for AD patients for 6 months totaled $3,129, whereas the indirect costs were $26,080. Patients with more-frequent symptoms used all healthcare resources, including the hospital, emergency room, and physicians, more often than those with less-frequent symptoms. Those with lower levels of physical and instrumental functioning also used the hospital and physicians more often than those with higher levels of physical and instrumental functioning. Caregivers of these more severely impaired patients spent more hours providing care and reported missing more work than those caring for higher-functioning patients. These relationships remained after controlling for potentially confounding factors. CONCLUSIONS: This large study of patients at all stages of AD shows that the direct and indirect costs of AD are considerably lower for patients with fewer symptoms. Longitudinal studies will determine the impact on the overall cost of care of interventions that reduce symptoms and maintain patients at earlier stages of the disease.     

阿尔茨海默病与血管性痴呆的非认知功能损害

目的　观察阿尔茨海默病与血管性痴呆的患者除认知功能异常外 ,是否存在非认知功能的异常。方法　根据DSM -Ⅳ阿尔茨海默病及血管性痴呆的诊断标准以及CDR的临床痴呆分级标准 ,对神经内科老年记忆障碍专科病房的 2 1例轻中度阿尔茨海默病及 2 5例血管性痴呆患者的非认知功能损害的临床表现进行了观察 ,包括情感反应、行为异常、人格变化及知觉异常。结果　阿尔茨海默病患者的非认知功能损害在情感障碍 (16例 ,76 % )、人格异常 (10例 ,48% )及知觉异常 (6例 ,2 9% )方面 ,明显多于血管性痴呆组 (分别为 10例 ,40 % ;1例 ,4% ;1例 ,4% )。结论　痴呆患者不仅有认知功能的损害 ,还有非认知功能的损害。阿尔茨海默病的非认知功能损害重于血管性痴呆 ,可能与两种痴呆的发病机制不同有关。