【作者】 李娜；

【导师】 张雪梅；

【作者基本信息】 哈尔滨医科大学 ， 神经病学（专业学位）， 2021， 硕士

【摘要】 背景及目的:血管性痴呆（Vascular dementia,VD）是一种由各种脑血管疾病（cerebrovascular diseases,CVD）引起颅脑神经功能障碍而产生的智能损害的综合征,是常见的老年痴呆类型之一,该病发病原因复杂,且临床表现多种多样,会显著降低老年患者的晚年生活质量,所以我们一定要争取做到对该病尽早发现、尽早诊断,这无疑会对VD的发生发展有着至关重要的意义。在神经内分泌及神经元细胞中分布着一种特有的酶,即神经元特异性烯醇化酶（Neuron specific enolase,NSE）,在患者大脑的细胞或组织存在损伤的情况下,神经元坏死崩解,NSE进入到了脑脊液与生物细胞间隙里,这种酶具备穿透血脑屏障进入到人体血液的能力,故在神经细胞损伤严重程度评价中是一项具有重要意义的检测指标。已有研究表明,NSE的存在与缺血性卒中等严重疾病的发生发展有着紧密的联系,并且,经过技术方式测试到的NSE越高,脑损害愈严重,故临床上有时将其作为检测是否有缺血性卒中发生的一种较为重要的标志物^[1]。但是关于NSE是否可以作为缺血性卒中引起VD的标志物的研究很少。故本研究的目的是通过对缺血性卒中引起的VD患者神经元特异性烯醇化酶水平研究,探讨其在VD诊断中的应用价值。方法:选取2018年1月至2018年12月于齐齐哈尔市第一医院神经内科住院治疗的急性缺血性脑卒中患者共计100例,分为VD（+）组（即血管性痴呆组）和VD（-）组（即无血管性痴呆组）,每组各50例,另设立健康对照组50例,来自同期同医院的健康体检者。VD的诊断为美国精神病协会第5版《精神疾病诊断与统计手册》中VD的确诊标准。对VD（+）与VD（-）组患者予以美国国立卫生院卒中量表（National Institute of Health Stroke Scale,NIHSS）评分以及TOAST分型,并且采集两组中所有患者的一般流行病学资料,以及相关危险因素的信息,对照两组间基础资料的差异性。在患者入院后24小时内,采集空腹静脉血,检测其血清中NSE含量。将急性缺血性脑卒中患者记为卒中组,与健康对照组比较NSE表达情况及表达差异。使用受试者工作特征曲线（receiver operating characteristic curve,ROC）评估血清NSE在缺血性卒中引起的VD中的诊断价值。同时使用简易精神状态检查表（Mini-mental State Examination,MMSE）对VD患者进行痴呆辅助诊断及严重程度分级,将VD（+）组分为轻度、中度及重度痴呆组,对各组间血清中NSE的表达情况进行比较。第八版《神经病学》教材中介绍了多种VD分型,主要包括:关键部位梗死性痴呆、多发梗死性痴呆（皮层血管性痴呆）、分水岭梗死性痴呆（低灌注性痴呆）、出血性痴呆、动脉硬化性脑病、以及伴随有白质脑病和皮质下梗死的常染色体显性遗传性脑动脉病,比较各种类型间NSE表达情况。结果:1.卒中组与健康对照组对比,卒中组血清NSE含量比健康对照组明显升高,（P<0.001）,具有统计学意义;VD（+）组NSE值为20.07±6.37μg/L,VD（-）组NSE值为8.94±3.28μg/L,VD（+）组较VD（-）明显升高,P<0.05,差异具有统计学意义。2.ROC结果显示血清NSE浓度在缺血性卒中引起的VD患者诊断中的曲线下面积为0.955,特异度88%,灵敏度为90%。3.在轻度、中度、重度痴呆组间血清NSE含量对比中,轻度痴呆组NSE浓度为15.24±3.50μg/L,中度痴呆组NSE浓度为21.30±5.13μg/L,重度痴呆组NSE浓度为29.19±5.85μg/L,对三组间差异进行分析,均有统计学意义（P<0.05）,重度痴呆组NSE浓度>中度痴呆组NSE浓度>轻度痴呆组NSE浓度,具有统计学意义（P<0.05）,但血清NSE的表达情况与痴呆类型无明显相关（P>0.05）。结论:1.缺血性卒中引起的VD患者血清中NSE的表达量明显升高,NSE在血清中的高表达可能与VD的发生密切相关;2.血清NSE可能作为缺血性卒中引起的VD诊断的生物学指标;3.缺血性卒中引起的VD患者的血清中NSE含量可能与VD严重程度呈正相关,而与VD类型可能无关。更多还原

【Abstract】 Background and Purpose Vascular dementia(VD)is a syndrome of intellectual impairment caused by cerebral nerve dysfunction caused by various cerebrovascular diseases(CVD).It is one of the common types of senile dementia.The causes of the disease are complex,and the clinical manifestations are diverse,which will significantly reduce the quality of life of elderly patients in their later years.Therefore,we must strive to find and diagnose the disease as early as possible,This will undoubtedly be of great significance to the occurrence and development of VD.A special enzyme,Neuron specific enolase(NSE),is distributed in neuroendocrine and neuron cells.When cells or tissues of the patient’s brain are damaged,the nerve structure distributive elements become necrotic and disintegrate,and NSE enters the gap between cerebrospinal fluid and biological cells.This enzyme has the ability to penetrate the blood-brain barrier into human blood,Therefore,it is a significant indicator in evaluating the severity of nerve cell injury.Previous studies have shown that the existence of NSE is closely related to the occurrence and development of severe diseases such as ischemic stroke.Moreover,the greater the NSE expression level tested by professional application technology,the more serious the level of brain damage.Therefore,it is sometimes used clinically as an important marker to detect whether there is ischemic stroke [1].However,there are few studies on whether NSE can be used as a marker of VD caused by ischemic stroke.Therefore,the purpose of this study is to explore the application value of neuron specific enolase in the diagnosis of VD by studying the level of neuron specific enolase in patients with VD caused by ischemic stroke.Methods A total of 100 patients with acute ischemic stroke hospitalized in the Department of Neurology of the First Hospital of Qiqihar from January 2018 to December 2018 were selected and divided into VD(+)group(vascular dementia group)and VD(-.The diagnosis and treatment of VD met the diagnostic criteria of VD in the Diagnostic and Statistical Manual of Mental Disorders,the 5th edition of the American Psychiatric Association.The patients with medical pain in the VD(+)and VD(-)groups were scored by the National Institute of Health Stroke Scale(NIHSS)and classified by TOAST,and the general epidemic infectious disease reference data of all patients with medical pain in the two groups,as well as relevant risk influencing factor data information were collected to compare the differences of basic reference data between the two groups.Fasting venous blood was collected within 24 hours after the admission of patients with medical pain to detect the content of NSE in their serum.The patients with acute ischemic stroke were recorded as stroke group,and the expression of NSE was compared with that of healthy control group.The receiver operating characteristic curve(ROC)was used to evaluate the diagnostic value of serum NSE in VD caused by ischemic stroke.At the same time,the mini mental state examination(MMSE)was used to assist the diagnosis and severity grading of dementia in VD patients.The VD(+)group was divided into mild,moderate and severe dementia groups,and the expression of NSE in serum of each group was compared.The eighth edition of Neurology introduced a variety of VD classifications,mainly including: infarct dementia in key areas,multiple infarct dementia(cortical vascular dementia),watershed infarct dementia(hypoperfusion dementia),hemorrhagic dementia,arteriosclerotic encephalopathy,and autosomal dominant hereditary cerebral artery disease accompanied by white matter encephalopathy and subcortical infarction.NSE expression among different types was compared.Results1.Compared with the healthy control group,the content of serum NSE in the stroke group was significantly higher(p < 0.001).The NSE value was 20.07 ± 6.37 μG/L in the VD(+)group,and 8.94 ± 3.28 μG/L in the VD(-)group.It was significantly higher in the VD(+)group than the VD(-)group(p < 0.05).2.ROC results showed that the area under the curve of serum NSE concentration in the diagnosis of VD caused by ischemic stroke was 0.955,the sensitivity was 90%,and the specificity was 88%.3.In the comparison of serum NSE content among the mild,the NSE value was15.24 ± 3.50g/L in the mild dementia group,21.30 ± 5.13 μ g/L in the moderate dementia group and 29.19 ± 5.85 μ g/L in the severe dementia group.There was significant difference among the three groups(p< 0.05).The NSE value of the severe dementia group was higher than that of the moderate dementia group and the mild dementia group(p< 0.05).There was no significant correlation between the type of dementia and the expression of serum NSE(p > 0.05).Conclusions1.The expression of NSE in serum of the VD patients caused by ischemic stroke was significantly increased.The high expression of NSE in serum may be closely related to the occurrence of VD.2.Serum NSE may be used as a biological index for the diagnosis of VD caused by ischemic stroke.3.The content of serum NSE in patients with VD caused by ischemic stroke may be positively correlated with the severity of VD,but maybe not correlated with the type of VD.更多还原