血浆黏度与脑白质疏松的相关性研究

目的探讨血浆黏度与脑白质疏松(LA)之间的相关性。方法选取正常对照组60例和LA组60例,收集2组的临床资料来评估LA相关可能的危险因素,进一步对血浆黏度进行多因素Logistic回归分析,并采用MRI的Fazekas方法对LA组进行分级,评估不同程度LA患者的血浆黏度水平差异。结果 LA组的年龄、三酰甘油及血浆黏度水平与对照组比较,差异有统计学意义(P<0.05),血浆黏度的增高与LA的发生相关(OR=1.298),当调整其他危险因素后,差异仍有统计学意义(P<0.05);且随着Fazekas评分增加,血浆黏度水平随之增加。结论血浆黏度水平和LA相关,可能是LA的独立危险因素,且随着LA程度的加重而增高。     

血清半胱氨酸蛋白酶抑制剂C、肌酐与脑梗死相关性的研究

目的 探讨血清半胱氨酸蛋白酶抑制剂C浓度、血清肌酐浓度对脑梗死发病的影响.方法 选择经临床、颅脑CT和(或)MRI确诊的脑梗死患者84例及同期体检正常者76例,酶联免疫法测定血清半胱氨酸蛋白酶抑制剂C浓度,苦味酸法测定肌酐浓度,观察血清半胱氨酸蛋白酶抑制剂C、肌酐与脑梗死发病的关系.结果 脑梗死组血清半胱氨酸蛋白酶抑制剂C的浓度[(1.69±0.60)mg/L]明显低于对照组[(2.00±0.67)mg/L],血清肌酐的浓度[(86.62±14.02)μmol/L]明显高于对照组[(80.88±13.71)μmol/L],比较差异均有统计学意义(P＜0.05).相关分析显示血清半胱氨酸蛋白酶抑制剂C与脑梗死呈负相关(r=-0.238,P=0.002),血清肌酐与脑梗死呈正相关(r=0.208,P=0.010).结论 血清半胱氨酸蛋白酶抑制剂C、肌酐与脑梗死发病相关,半胱氨酸蛋白酶抑制剂C可能是脑梗死发病的一种保护因素,而肌酐可能是脑梗死发病的一种危险因素.     

脑白质疏松患者肾功能不全与血浆同型半胱氨酸的相关性研究

目的探讨脑白质疏松(leukoaraiosis,LA)合并肾功能不全与血浆Hcy水平的相关性。方法选取LA患者作为研究对象,依据病史及肾功能检测指标将患者分为肾功能不全组(观察组)和肾功能正常组(对照组)。记录患者Cr、BUN、UA、Hcy、HbA1c、TC、LDL-C等生化指标水平,并以Fazekas评分量表完成LA严重程度评分。对比2组生化指标水平,并对肾功能不全的可能影响因素进行多因素分析。对生化指标、肾功能及LA进行相关性分析。结果共入组186例患者,其中对照组112例,观察组74例。①与对照组相比,观察组BUN水平(P=0.001)、Cr水平(P=0.000)、UA水平(P=0.000)、Hcy水平(P=0.000)升高,差异有统计学意义;观察组Fazekas评分较对照组升高,差异有统计学意义(P=0.04);②相关分析显示,血浆Hcy水平与Fazekas总评分(r=0.202,P=0.027)、Cr水平(r=0.458,P<0.001)、UA水平(r=0.229,P=0.010)、BUN水平(r=0.178,P=0.046)正相关;③多因素Logistic回归分析显示,Hcy(OR 4.165,95%CI 1.138～15.249,P=0.031)是LA患者肾功能不全的危险因素。结论 Hcy是LA患者肾功能不全的危险因素,肾功能不全可能通过影响血浆Hcy水平从而参与LA的发生发展。     

血清同型半胱氨酸和半胱氨酸蛋白酶抑制剂C水平变化与脑卒中的相关性分析

目的 探讨血清同型半胱氨酸和半胱氨酸蛋白酶抑制剂C在脑卒中发生发展过程的关系,以及二者与脑卒中传统危险因素的相关性。方法 选择2011-05—2013-06我院收治的脑卒中患者77例,其中脑出血38例,脑梗死39例;另选取我院体检中心同期体检的健康人员77例为对照组。测定各组血脂、血清同型半胱氨酸(Hcy)、半胱氨酸蛋白酶抑制剂C(Cys-C)、血肌酐(SCr)、尿酸(UA)等相关指标,比较各组指标相关性。结果 脑卒中患者Hcy、Cys C、SCr、UA、TC、TG均显著高于对照组(P<0.05),2组HDL-C比较差异无统计学意义(P>0.05)。Pearsman相关显示Hcy与Cys C、SCr、UA呈正相关,Cys C与SCr、Cys C与UA呈正相关(P<0.05),Hcy与TC、TG、LDL-C、HDL-C及NIHSS不具备相关性;Cys C与TC、TG、LDL-C、HDL-C及NIHSS不具备相关性(P>0.05)。结论 Hcy、Cys C为脑卒中患者的危险因素,且独立于血脂、神经功能损伤等指标,联合检测HCY、Cys C、SCr、UA等指标对脑卒中诊断有辅助价值。     

半胱氨酸蛋白酶抑制剂C与缺血性脑卒中的关系研究

肾功能不全是缺血性脑卒中重要危险因素之一,而半胱氨酸蛋白酶抑制剂C(cystatin C,cys C)是目前检测肾功能的灵敏指标。cys C作为最主要的内源性组织蛋白酶抑制剂,参与炎症、动脉粥样硬化及心脑血管疾病的病理、生理过程;可预测急性冠状动脉综合征的发生和预后,预测冠心病患者冠状动脉病变的广度、心力衰竭及全因死亡的风险。但在缺血性脑卒中方面cys C是缺血性脑卒中的危险因素还是保护因素目前仍存在争议。明确其与缺血性脑卒中的联系,可为缺血性脑卒中的早期预防和治疗提供参考。     

阿尔茨海默病与脑白质疏松血浆同型半胱氨酸水平的相关性研究

目的探讨阿尔茨海默病(AD)与缺血性脑白质疏松症(LA)、血浆同型半胱氨酸(Hcy)及叶酸、维生素B₁₂水平的相关性。方法采用简易智能状态量表(mini-mental state examation,MMSE)检查患者的认知功能,根据MMSE评分和AD的诊断标准收集病例,共收集AD患者60例,正常对照组64例。通过头颅MRI检查筛选LA病例,AD伴LA者36例,无LA的AD患者24例;对照组无LA 40例,伴LA的正常对照组24例;用化学免疫发光法测定2组血浆同型半胱氨酸、叶酸、维生素B₁₂水平,同时检测所有受试者的血压、血糖、血脂、体重指数、教育情况等。结果与对照组比较,AD组血浆同型半胱氨酸升高(P<0.05),叶酸和维生素B₁₂水平下降(P<0.05);通过应用R×C资料的卡方检验得出AD组与对照组脑白质疏松发生率差异有统计学意义(P=0.010);对AD组脑白质疏松和认知障碍程度进行Spearman相关性分析得出,AD组认知障碍程度与脑白质疏松程度呈正相关(r_s=0.430,P=0.010)。结论高Hcy可能参与AD的发病,而LA发生加重了认知功能损伤,适当补充叶酸和维生素B₁₂可有助于改善痴呆患者的临床症状。     

无残障老年人脑白质疏松与脑萎缩的相关性研究

目的对两种评估脑白质疏松的方法进行比较,探讨脑白质疏松与脑萎缩的关系。方法 45例磁共振成像（MRI）提示脑白质疏松但无残障的老年住院患者。应用评价胆碱能神经纤维通路脑白质疏松CPHIS量表和全脑白质疏松Scheltens量表分别评估头颅MRI脑白质疏松的严重程度,并与脑萎缩指标进行Spearman相关分析。结果 45例无残障脑白质疏松患者CPHIS量表评分（27.18±20.26）,Scheltens量表评分（19.87±11.69）。脑白质疏松CPHIS评分与皮层脑沟宽度呈正相关（r=0.341,P〈0.05）;Scheltens量表评分与脑室指数呈正相关（r=0.320,P〈0.05）,与皮层脑沟宽度呈正相关（r=0.325,P〈0.05）。结论皮层脑萎缩主要与胆碱能神经纤维的脑白质疏松有关。     

高同型半胱氨酸、高纤维蛋白原等与Binswanger病脑白质疏松严重程度的相关性

目的 探讨高同型半胱氨酸(Hcy)、高纤维蛋白原(Fib)等对Binswanger病(BD)脑白质疏松(LA)严重程度的影响.方法 对自2005年1月1日至2011年5月9日在中山大学附属第三医院住院且确诊为BD的患者进行血清Hcy、Fib、低密度脂蛋白(LDL)、载脂蛋白A(Apoa)、载脂蛋白B(Apob)、高密度脂蛋白(HDL)检测,并将BD患者按LA头颅MRI表现严重程度分为轻、中、重3型,单因素分析及有序Logistic回归法分析Fib、Hcy等因素与LA严重程度的关系.结果 单因素分析结果显示:LA不同严重程度组间性别、年龄、高血压病、卒中史、高脂血症比较差异有统计学意义(P＜0.05).LA严重程度与Hcy、Fib存在正向的等级相关关系(P＜0.05).有序Logistic回归分析结果显示:女性LA程度比男性更严重;年龄越大,有卒中史和Fib测定值越大,LA程度更严重(P＜0.05).结论 Fib水平是BD恶化的一个重要因素,降低Fib水平可能对延缓BD病情进展有效.     

脑梗死合并脑白质疏松相关因素分析

目的探讨脑白质疏松(leukoaraiosis,LA)的主要发病因素与发病机制,以达到降低发病率及预防脑梗死的目的。方法收集2013-10—2015-10在我院神经科住院的脑梗死患者,根据典型影像学改变分为LA组与非LA组。对比2组可能危险因素。采用SPSS 17.0软件和S-PLUS 8.0软件,先对可能的危险因素行单因素分析,再用Logistic回归对初步筛选出的危险因素行多因素分析。比较LA的严重程度与筛选出的相关因素的关系。结果 (1)2组间危险因素的单因素分析显示,年龄、体重指数、冠心病、血红蛋白、同型半胱氨酸、脑梗死分型比较差异有统计学意义(均P0.05)。(2)多因素Logistic回归分析显示,年龄(OR=1.142,95%CI:1.052~1.239,P=0.001)和同型半胱氨酸(OR=1.212,95%CI:1.023~1.436,P=0.026)是LA的独立危险因素。(3)Bootstrap法估计相加交互作用指标的可信区间显示,年龄和同型半胱氨酸与LA的发病存在正相加交互作用[RERI=0.01487(95%CI:0.000 32~0.061 15)、AP=0.011 14(95%CI:0.000 61~0.03563)、S=1.047(95%CI:1.012 70~1.081 76)]。(4)有序多分类Logistic回归分析显示,年龄(β=0.093,95%CI:0.056~0.129,P=0.000)越大,LA程度越严重;LA程度越严重,MMSE评分(β=-0.137,95%CI:-0.189~-0.085,P=0.000)越低。结论 (1)年龄和同型半胱氨酸是LA的两个独立危险因素。(2)年龄和同型半胱氨酸与LA的发病存在正相加交互作用,即这两因素的联合作用大于单独作用之和。(3)年龄越大,LA程度越严重。(4)LA程度越严重,认知功能障碍越明显。(5)LA的发病机制不清楚,可能与脑小血管病变有关。     

老年人脑白质疏松的相关危险因素

目的探讨老年人脑白质疏松(LA)的相关危险因素。方法采集轻度组、中度组及重度组患者的临床资料,并检测其血浆同型半胱氨酸(Hcy)水平。结果轻度组、中度组、重度组的年龄、男性及高血压比例差异有统计学意义(均P0.05),而糖尿病、冠心病、高脂血症及吸烟比率差异均无统计学意义。3组间血浆Hcy水平及高Hcy血症(HHcy)患者比率差异有统计学意义(均P0.01)。多因素分析显示,年龄(OR=1.078,95%CI:1.034~1.123,P=0.000)、男性(OR=2.601,95%CI:1.441~4.692,P=0.002)、高血压(OR=2.672,95%CI:1.493~4.783,P=0.001)、Hcy(OR=1.035,95%CI:1.009~1.059,P=0.007)及HHcy(OR=1.954,95%CI:1.055~3.618,P=0.033)是LA独立危险因素。结论 HHcy、年龄、男性、高血压是老年人LA的独立危险因素。     

Cystatin C expression in ischemic white matter lesions

Objectives –  To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs).
Materials and methods –  Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls.
Results –  Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(−)] were lower than those in 38 patients with grade 0–1 ( P  = 0.0022 and P  < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls ( P  = 0.0027) and in the mild WML group ( P  = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1β increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes.
Conclusions –  These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.     

急性缺血性卒中患者血清胱抑素C水平与脑白质疏松严重程度的相关性研究

目的探讨急性缺血性卒中患者血清胱抑素C水平与脑白质疏松严重程度的相关性。方法选择192例行头颅MRI检查的急性缺血性卒中患者,应用Fazekas评分量表将合并脑白质疏松的急性缺血性卒中患者分为轻度组27例,中度组96例,重度组69例。收集3组患者包括血清胱抑素C水平在内的各项临床资料。结果年龄、三酰甘油、肌酐等在3组间比较差异有统计学意义(均P<0.05),轻度组、中度组、重度组血清胱抑素C水平依次升高,差异均有统计学意义(均P<0.05)。有序多分类Logistic回归分析显示血清胱抑素C水平是脑白质疏松严重程度增加的独立危险因素(OR=4.669,P=0.042);Spearman相关分析显示,血清胱抑素C水平与脑白质疏松严重程度呈正相关(r=0.371,P=0.000)。结论血清胱抑素C水平升高与急性缺血性卒中患者脑白质疏松的严重程度独立相关。     

脑白质疏松症及其临床意义

脑白质疏松症（LA）是一个影像学术语，在老年人中较为常见。本文对LA近年来的相关研究进展予以介绍。     

脑白质疏松的临床意义

分析４０例痴呆患者、１２０例无痴呆脑血管病患者及６０例临床既无痴呆也无脑血管病病史的“正常”老人ＣＴ和ＭＲＩ资料，脑白质疏松的发生率由高到低依次为痴呆（６２．５０％）、脑血管病（３４．１７％）和“正常”老人（１５．００％）。推测脑白质疏松的病理生理基础是脑室周围半卵圆区缺血、缺氧及炎症反应所致脑白质神经纤维脱髓鞘。脑白质疏松可能加重或导致智能障碍。     

血压及其变异性与脑白质疏松症的相关性研究进展

脑白质疏松症是指脑室周围或皮质下区(半卵圆中心)弥漫性非特异性白质损害。脑白质疏松症可以增加脑卒中的风险,并与认知功能下降和运动障碍等密切相关。已有研究认为高血压病是脑白质疏松症最主要的危险因素。但随着对脑白质疏松症形成的病理生理机制研究的不断完善,学者们发现低血压及血压变异性也与脑白质疏松症相关。文中旨在对血压及其变异性与脑白质疏松症之间的联系研究进行综述。     

Leukoaraiosis is associated with arterial wall thickness: A quantitative analysis

Leukoaraiosis refers to an age‐related, abnormal appearance of the brain white matter on neuroimaging. The association between leukoaraiosis and cerebrovascular disease suggests that ischemia may be an important contributing factor; however, the pathogenesis of the condition remains controversial. We hypothesized that physical abnormalities of blood vessels might be culpable and compared the external and internal measurements of blood vessel walls between brains that demonstrated leukoaraiosis on imaging and normal control brains. Fourteen brains of individuals who had been diagnosed as having severe leukoaraiosis and five non‐leukoaraiosis control brains were studied. Arterial cross‐sections were evaluated by length measurements with an image analysis device. Arterial wall thickness and the ratio of the outer and inner diameters of the vessel were measured. We measured a total of 108 vessels in the leukoaraiosis group and 95 vessels in the control group. The vessel walls of the leukoaraiosis patients were an average of 5.5 µm thicker than the walls of control vessels of the same inside diameter (P = 0.0000, 95% CI 3.01–8.08) and an average of 2.3 µm thicker than walls of control vessels of the same outside diameter (P = 0.016, 95% CI 0.48–4.17). Our data provide evidence that leukoaraiosis is associated with vessel wall thickening in an additive fashion and indicate that structural vascular abnormalities are associated with leukoaraiosis.     

Leukoaraiosis is associated with genes regulating blood–brain barrier homeostasis in ischaemic stroke patients

Background: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. Methods: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30 104 genotypes. Seventy‐nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa ) was used to examine the role of the identified genes. Results: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34–17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15–0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38–11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25–0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36–4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212‐AA of ITGB6 and rs2290608‐GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10⁻⁴) and (ii) Fazekas (P = 4.5 × 10⁻⁵). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood–brain barrier (BBB) homeostasis. Conclusions: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.