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血清胱抑素C水平与血管性认知功能障碍的相关性研究

摘要 / Abstract:

目的 探讨血清胱抑素C(Cys-C)水平与血管性认知功能障碍的相关性,并分析其在发生血管性认知功能障碍中的意义。方法 选择2014-02-30—2017-07-30于郑州人民医院神经内科住院的110例血管性认知功能障碍患者(认知障碍组),选取同期90例健康体检者为对照组。抽取空腹静脉血5 mL,使用免疫比浊法检测血Cys-C水平,比较2组一般资料及Cys C水平,分析血管性认知障碍的独立危险因素。结果 2组年龄、性别、吸烟史、高血压史、糖尿病史、TC、血肌酐、血糖、Cys-C水平差异有统计学意义(P

关键词 / KeyWords:

血管性认知功能障碍,血清胱抑素C,危险因素,发病机制,相关性

血清胱抑素C水平与血管性认知功能障碍的相关性研究

刘海涛1)  张淑玲1)△   白宏英2)
1)郑州人民医院神经内科一病区,河南 郑州 450000  2)郑州大学第二附属医院,河南 郑州 450014
作者简介:刘海涛,主治医师,Email:liujc258@163.com
通信作者:张淑玲,主任医师,Email:zsl66317@163.com
摘要  目的  探讨血清胱抑素C(Cys-C)水平与血管性认知功能障碍的相关性,并分析其在发生血管性认知功能障碍中的意义。方法  选择2014-02-30—2017-07-30于郑州人民医院神经内科住院的110例血管性认知功能障碍患者(认知障碍组),选取同期90例健康体检者为对照组。抽取空腹静脉血5 mL,使用免疫比浊法检测血Cys-C水平,比较2组一般资料及Cys C水平,分析血管性认知障碍的独立危险因素。结果  2组年龄、性别、吸烟史、高血压史、糖尿病史、TC、血肌酐、血糖、Cys-C水平差异有统计学意义(P<0.05)。血管性认知功能障碍患者年龄、TC、血肌酐、血糖、Cys-C水平,以及男性比例、吸烟史、高血压史、糖尿病史比例高于对照组。Logistic回归分析示,Cys-C、TC、高血压史、糖尿病史、年龄是血管性认知功能障碍的独立影响因素(P<0.05)。结论  Cys-C水平升高是血管性认知功能障碍的独立危险因素,高水平Cys-C可能与血管性认知功能障碍的发生具有密切关系,需进一步研究证实。
关键词】  血管性认知功能障碍;血清胱抑素C;危险因素;发病机制;相关性
中图分类号】  R749.13    【文献标识码】  A    【文章编号】  1673-5110(2018)10-1057-06  DOI:10.12083/SYSJ.2018.10.264
Relationship between serum cystatin C level and vascular cognitive impairment
LIU Haitao1),ZHANG Shuling1),BAI Hongying2)
1)Department of Neurology,Zhengzhou People's Hospital,Zhengzhou 450000,China;2)The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,China
Abstract】  Objective  To investigate the relationship between the level of serum cystatin C (Cys-C) and the vascular cognitive impairment,and and analyze its significance in the development of vascular cognitive impairment.Methods  From January 30,2014 to July 30,2017,110 patients with vascular cognitive impairment who were hospitalized in the Neurology Department of Zhengzhou People's Hospital were selected as the cognitive impairment group,and 90 cases of health checker were selected for the same period as the control group.Five milliliter of venous blood was taken to detect the level of Cys-C by immunoturbidimetry.The general data and the level of Cys-C were compared between two groups,and independent risk factors for vascular cognitive impairment were analyzed.Results  The differences in age,gender,smoking history,hypertension history,diabetes history,the levels of TC,serum creatinine,blood glucose,and Cys-C were statistically significant between two groups (P<0.05).The age,levels of TC,serum creatinine,blood glucose and Cys-C were higher in patients with vascular cognitive impairment than in normal patients.The proportion of male patients,smoking history,hypertension history,and diabetes history were higher in patients with vascular cognitive impairment than those in normal subjects.Logistic regression analysis showed that Cys-C,TC,history of hypertension,history of diabetes,and age were independent influencing factors of vascular cognitive impairment (P<0.05).Conclusion  The elevated level of Cys-C is an independent risk factor for vascular cognitive impairment.High levels of Cys-C may be closely related to the occurrence of vascular cognitive impairment,which needs further research to confirm.
Key worlds】  Vascular cognitive impairment;Serum cystatin C;Risk factors;Pathogenesis;Relationship
        血管认知功能障碍是由血管疾病引起的异常认知状态,好发于老年人群,患者认知缺陷严重不足,但未达到痴呆标准,基本功能不会丧失。早期识别和治疗血管性认知障碍尤为重要[1-3]。研究显示,寻找准确的生物标志物以及危险因素,用于早期诊断以及预防血管性认知障碍,对临床探索血管性认知障碍发病机制、疾病特点以及临床治疗具有重要意义[4-5]。血清胱抑素C(Cys-C)是一种由Cys C(CST3)基因编码,由人体组织分泌的半胱氨酸蛋白酶抑制剂,近年来,其在血管认知功能障碍以及阿尔茨海默病中的研究越来越多[6-8]。作为肾功能的生物标志物,其也是血管认知功能障碍的有效预测因子[9-10]。多种证据表明,Cys C具有抗炎功能,并对年龄相关疾病发挥保护作用[11-13]。目前,临床对于血管性认知功能障碍的影响因素结论并不统一。本研究探讨血清Cys-C水平与血管性认知功能障碍的相关性,并分析其在发生血管性认知功能障碍中的意义。
1  资料与方法
1.1  研究对象  选择2014-02-30—2017-07-30于郑州人民医院神经内科住院的110例血管性认知功能障碍患者(认知障碍组),选取同期90例健康体检者为对照组。男127例,女73例,年龄35~77(53.8±6.4)岁。记录2组基础资料(年龄、吸烟史、饮酒史、性别、高血压史等)。本研究经过我院伦理委员会审核,患者或其家属对研究内容知情且签订书面同意书。
1.2  纳入排除标准  纳入标准:(1)认知障碍组患者均接受蒙特利尔认知评估量表(MoCA,共7个项目,满分30分,≥26分为正常)评估认知功能[14],且MoCA评分<26分;(2)认知障碍组患者头颅MRI或CT提示存在脑缺血病灶;(3)对照组MoCA评分≥26分。排除标准:(1)先天性疾病或精神病引起的身体残疾;(2)合并阿尔茨海默病;(3)疼痛综合征、晚期糖尿病、恶性肿瘤、肾衰竭、肝功能衰竭、严重贫血者;(4)甲状腺功能异常者;(5)正在接受认知障碍治疗者;(6)严重交流障碍者。
1.3  检测方法  入院后清晨抽取空腹5 mL静脉血,样品收集1 h内以3 000 r/min离心10 min,分离血浆。实验室检测前,将分离的血浆储存在-30 ℃冰箱内。使用Behring BN ProSpec分析仪(Dade Behring)检测Cys C(免疫比浊法)、血糖、甘油三酯(TC)、血肌酐、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)等水平。所有检测结果重复3次。
1.4  观察指标  比较2组一般资料以及Cys C水平,分析血管性认知功能障碍的独立危险因素。
1.5  统计学分析  使用SPSS 13.0进行数据统计,符合正态分布的定量资料使用均数±标准差(x±s)表示,组间比较用t检验,定性资料以百分数表示,用χ2检验或Fisher精确概率法,相关性利用Pearson相关分析法,二分类Logistic回归分析用于分析血管性认知功能障碍的独立危险因素,以双侧P<0.05为差异有统计学意义。
2  结果
2.1  2组临床资料比较  2组年龄、性别、吸烟史、高血压史、糖尿病史、TC、血肌酐、血糖、Cys-C水平差异有统计学意义(P<0.05)。血管性认知功能障碍患者年龄、TC、血肌酐、血糖、Cys-C水平,以及男性比例、吸烟史、高血压史、糖尿病史比例高于对照组。见表1。
2.2  多因素分析  Logistic回归分析示,Cys-C、TC、高血压史、糖尿病史、年龄是血管性认知功能障碍的独立影响因素(P<0.05)。高水平Cys-C、TC、高龄以及合并高血压史、糖尿病史是血管性认知功能障碍的独立危险因素。见表2。
3  讨论
        认知功能障碍是老年群体高发疾病。近年来,随着人口老龄化进程加快,发病率呈现上升趋势,是引起老年痴呆的第2大疾病,严重影响其健康和生活质量[15-16]。大多数认知功能障碍患者存在多发性脑梗死或脑白质缺血,如未得到及时有效治疗,多数患者最终发展为痴呆[17-23]。血管性认知功能障碍包括各种脑血管疾病引起的认知障碍,如脑出血、脑栓塞、脑血流灌流异常等。Cys-C是由Cys C(CST3)基因编码的Cys超家族成员,属于内源性组织蛋白酶抑制物,可抑制蛋白酶B,具有平衡血管壁内组织蛋白酶、抗蛋白酶活性的作用[18]。早期研究重点为Cys-C作为肾功能的生物标志物,在肾脏疾病中起作用。近年来,其在血管性认知功能障碍以及阿尔茨海默病中的研究越来越多[19]。已有研究证实,Cys-C与脑血管病变具有显著相关性,Cys C不仅可调节痴呆,还与血管功能相关,并介导血管舒张、炎症和氧化应激等反应[24-30]
表1  2组临床资料比较
资料 n 认知障碍组(n=110) 照组(n=90) χ2/t P
年龄       4.49 0.034
  45 88 47(52.2) 41(37.3)    
  <45 112 43(47.8) 69(62.7)    
吸烟史       6.738 0.009
  有 56 39(35.5) 17(18.9)    
  无 144 71(64.5) 73(81.1)    
性别       5.79 0.016
  男 127 78(70.9) 49(54.4)    
  女 73 32(29.1) 41(45.6)    
高血压       5.137 0.023
  有 51 35(31.8) 16(17.8)    
  无 149 75(68.2) 74(82.2)    
糖尿病       11.585 0.001
   有 36 29(26.4) 7(7.8)    
   无 164 81(73.6) 83(92.2)    
TG(mmol/L)   1.42±0.53 1.59±0.71 1.937 0.054
TC(mmol/L)   3.11±1.52 1.55±0.80 9.307 0
HDL-C(mmol/L)   1.06±0.17 1.07±0.16 0.452 0.651
LDL-C(mmol/L)   2.85±0.61 2.95±0.79 1.01 0.314
肌酐(μmol/L)   94.66±14.02 60.87±10.94 18.678 0
Cys-C(mg/L)   1.54±0.38 1.21±0.28 6.854 0
表2  血管性认知功能障碍的Logistic回归分析结果
变量 B OR 95% CI P
年龄 0.879 1.214 1.0561.947 0.032
高血压史 0.927 1.442 1.1212.541 0.022
糖尿病史 0.745 1.103 1.0231.547 0.046
Cys-C(mg/L) 2.141 8.147 1.59746.314 0.001
TC(mmol/L) 0.946 1.624 1.2476.541 0.007
        ZHANG等[31]分析了阿尔茨海默病脑组织中淀粉样沉积物成分时发现Cys-C,提示Cys-C可能参与了神经组织损伤。已有研究证实,Cys-C基因多态性与阿尔茨海默病、认知功能障碍具有相关性[5,20]。本研究显示,血管性认知功能障碍患者Cys-C水平高于正常体检者;此外,2组年龄、性别、吸烟史、高血压史、糖尿病史、TC、血肌酐、血糖差异有统计学意义(P<0.05)。血管性认知功能障碍患者年龄、TC、血肌酐、血糖、Cys-C水平,以及男性比例、吸烟史、高血压史、糖尿病史比例高于正常体检者。Logistic回归分析示,Cys-C、TC、高血压史、糖尿病史、年龄是血管性认知功能障碍的独立影响因素(P<0.05)。高水平Cys-C、TC、高龄以及合并高血压史、糖尿病史是血管性认知功能障碍的独立危险因素。ZUO等[32-35]研究不同类型痴呆症(血管性认知功能障碍和阿尔茨海默病)患者的Cys C和HDL水平,调查Cys C和HDL是否与不同类型痴呆的严重程度和患病率相关,结果显示,与健康对照组相比,血管性认知功能障碍患者血浆Cys C水平较高,HDL水平较低,血浆Cys C/HDL对痴呆具有诊断价值。本研究中血管性认知功能障碍Cys C水平较健康体检者高,与相关研究[36-38]一致。HDL是存在于全身循环和脑中脂蛋白颗粒的异质组的一部分,主要分别促进脂质和脂质相关分子从体内和整个身体的清除和递送。有证据表明,血浆HDL及其主要蛋白质组分ApoA-Ⅰ也具有有效的血管保护特性,如促进血管功能改善,抑制炎症,抑制内皮修复,防止脂质氧化和刺激内皮修复[10,39]。本研究中,2组HDL差异无统计学意义,可能与纳入患者种族差异、检测方法以及纳入标准差异有关。研究认为,Cys C可能在痴呆发病机制中起重要作用,血浆Cys C水平可能是区分血管性认知功能障碍与健康受试者的有效筛选工具[17]
        在排除混杂影响因素后,本研究显示,高水平Cys-C、TC、高龄以及合并高血压史、糖尿病史是血管性认知功能障碍的独立危险因素。刘利红等[24]分析了411例血管性认知功能障碍的危险因素,结果显示,Cys-C是血管性认知功能障碍的独立危险因素,与本研究一致。此外,RAFAILIDIS等[40]研究认为,血管危险因素,如年龄、TC、高血压史、糖尿病史等增加血管性认知功能障碍的发病率,并促进其向痴呆发展。血清Cys-C水平异常可促进动脉粥样硬化发生,动脉硬化狭窄影响脑组织血供;此外,动脉损伤促进炎性细胞因子释放,造成脑组织损伤;Cys-C可通过血脑屏障参与脑部炎症反应,促进认知功能障碍发展[41-43],本研究进一步证实了Cys-C在血管性认知功能障碍中作用。
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(收稿 2018-04-27  修回2018-05-09)
本文编辑:夏保军
本文引用信息:刘海涛,张淑玲,白宏英.血清胱抑素C水平与血管性认知功能障碍的相关性研究[J].中国实用神经疾病杂志,2018,21(10):1057-1062.DOI:10.12083/SYSJ.2018.10.264
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