1型糖尿病患者血清HMGB1与认知功能及脑功能影像的相关性研究
发布时间：2018-04-17 06:34
本文选题：1型糖尿病 + 高迁移率族蛋白B1 ； 参考：《郑州大学》2017年硕士论文
【摘要】：目的本文通过神经心理学量表测验1型糖尿病(T1DM)患者的认知功能改变,利用氢质子磁共振波谱分析(1H-MRS)、静息态功能磁共振(rs-fMRI)扫描量化分析T1DM患者的海马代谢物、脑功能连接改变,并通过酶联免疫吸附法(ELISA)检测血清中高迁移率族蛋白B1(HMGB1)等炎症因子,结合糖化血红蛋白(HbA1C)、血糖波动参数等,以期发现T1DM患者是否出现认知功能改变及其大脑结构基础、早期生物学指标及危险因素。方法1.本研究分为两组,T1DM组:30例1型糖尿病患者,来自郑州大学人民医院内分泌代谢科的住院患者,正常对照组:36例健康对照者,来自郑州大学人民医院体检中心的健康体检者。2.收集受试者临床资料,并采用ELISA测定受试者血清中HMGB1、白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)的浓度,应用72h动态血糖监测仪监测,评估T1DM患者的血糖波动。3.采用神经心理学量表测验受试者认知功能:数字符号替换测验(DSST)、数字广度测验(DST)、连线测验(TMT)、Rey听觉词语学习测验(RAVLT)、Rey-Osterrieth复杂图形测验(ROCF),评估受试者信息处理速度、注意力、执行功能、记忆、视空间能力。4.受试者行头颅核磁共振扫描,通过1H-MRS测定海马N-乙酰天冬氨酸(NAA)、胆碱复合物(Cho)、肌酸(Cr)的浓度;采用rs-fMRI扫描,后行全脑范围的Granger因果分析,以测定脑区间的功能连接。5.SPSS 19.0统计软件进行数据分析。结果1.两组间临床资料、炎症因子的比较T1DM组与正常对照组相比,年龄、性别、受教育程度、吸烟史、BMI差异无统计学意义(P0.05),LDL-C低于正常对照组(P0.05),HMGB1、IL-1β、TNF-α、IL-6均高于正常对照组(P0.05)。2.T1DM组患者的病程、HbA1C、血糖波动参数T1DM组患者病程9.2±6.0年,HbA1C:9.44±2.41%,平均血糖(MBG):9.43±2.44mmol/l,平均血糖波动幅度(MAGE):6.20±2.24mmol/l,日间血糖平均绝对差(MODD):3.87±1.58mmol/l,血糖标准差(SDBG):2.39±0.85mmol/l,低血糖指数(LBGI):2.50±2.44,血糖低于3.9mmol/l百分比(glu70):3.37±3.88%。3.两组间认知功能、海马代谢物、脑功能连接的比较T1DM组与正常对照组相比,DSST、RAVLT(1-5)测验总和、ROCF临摹低于正常对照组(P0.05);左侧海马NAA/Cr低于对照组(P0.05),右侧海马NAA/Cr、双侧海马Cho/Cr差异无统计学意义(P0.05);以左测海马(HIP.L)为种子点,GC外向流中,T1DM组自HIP.L到右侧角回、顶上回及韦尼克区的部分脑区的连接较正常对照组增强(P0.05),GC内向流中,T1DM组自额上回、额中回、中央前回、中央后回、辅助运动区、楔叶、左侧枕上回到HIP.L的连接较正常对照组减弱(P0.05)。4.T1DM组Pearson、Spearman相关性分析及多元回归分析认知功能与其他指标的相关性分析示:受教育程度、HbA1C、MAGE、SDBG、HMGB1、TNF-α、右侧海马Cho/Cr与DSST相关(P0.05),MODD、SDBG与DST相关(P0.05),受教育程度、MAGE、HMGB1、TNF-α与TMT-B相关(P0.05),受教育程度、MAGE、SDBG、HMGB1、IL-1β、IL-6、左侧海马NAA/Cr与RAVLT(1-5)测验总和相关(P0.05),HMGB1、IL-1β、IL-6与RAVLT延迟回忆相关(P0.05),年龄、LBGI与ROCF临摹相关(P0.05)。HbA1C、血糖波动参数与HMGB1的相关性分析示:HbA1C与HMGB1无相关关系(P0.05),MAGE与HMGB1相关(P0.05)。HMGB1与其他炎症因子的相关性分析示:HMGB1与IL-1β、TNF-α、IL-6相关(P0.05)。HbA1C、血糖波动参数、HMGB1与海马代谢物的相关性分析示:MODD、glu70与左测海马NAA/Cr相关(P0.05),glu70与左测海马Cho/Cr相关(P0.05),HbA1C、HMGB1与海马组织中代谢物质无明显相关性(P0.05)。多元回归分析:以认知功能测验为因变量,其他指标为自变量,行多元回归分析示:DSST的危险因素是受教育程度、HbA1C、SDBG、HMGB1;DST的危险因素是HbA1C、MODD;TMT-B的危险因素是受教育程度、HMGB1;RAVLT(1-5)测验总和的危险因素是MAGE、SDBG、左侧海马NAA/Cr;RAVLT延迟回忆的危险因素是MODD、HMGB1;ROCF临摹的危险因素是年龄、HMGB1、左侧海马NAA/Cr。结论1.1型糖尿病患者信息处理速度、记忆、视空间能力下降。2.1型糖尿病患者左侧海马与多个脑区功能连接异常,NAA下降是短时记忆的危险因素,提示脑功能影像改变可能是1型糖尿病相关认知功能下降的结构基础。3.HbA1C、血糖波动是1型糖尿病患者认知功能下降的危险因素,可能通过促进HMGB1等炎症因子分泌,参与1型糖尿病相关并发认知功能下降的发生机制。
[Abstract]:The purpose of this paper through the neuropsychological tests of type 1 diabetes mellitus (T1DM) changes in cognitive function and proton magnetic resonance spectroscopy (1H-MRS), using resting state functional magnetic resonance imaging (rs-fMRI) scanning quantitative analysis of hippocampal metabolite T1DM patients, brain functional connectivity changes, and by enzyme-linked immunosorbent assay (ELISA) high mobility group protein B1 in serum (HMGB1) and other inflammatory factors, combined with glycosylated hemoglobin (HbA1C), blood glucose fluctuation parameters, in order to find out whether T1DM patients with cognitive function and brain structure, early biological markers and risk factors. Methods 1. patients were divided into two groups, group T1DM: 30 cases patients with type 1 diabetes inpatients from Zhengzhou University people's hospital endocrine metabolism section, normal control group: 36 healthy subjects and healthy subjects.2. were collected from medical examination center of people's Hospital of Zhengzhou University The clinical data, and the ELISA was tested by serum HMGB1, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF- alpha) concentration, the application of 72h dynamic blood glucose monitoring, blood glucose fluctuation.3. assessment in patients with T1DM cognitive function using neuropsychological testing participants: the digit Symbol Substitution Test (DSST), digital span test (DST), trail making test (TMT), Rey auditory verbal learning test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCF), the evaluation of subjects with information processing speed, attention, executive function, memory, visual spatial ability.4. subjects MRI, determined by 1H-MRS N- in the hippocampus of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) concentration; by rs-fMRI scan, Granger causality analysis was to determine the scope of the whole brain, brain functional connectivity interval.5.SPSS 19 statistical software for data The results of analysis. 1. clinical data between the two groups, inflammatory factor T1DM group compared with normal control group, age, gender, education level, smoking history, there was no significant difference of BMI (P0.05), LDL-C lower than the normal control group (P0.05), HMGB1, IL-1 beta, TNF- alpha, IL-6 were higher than that of normal control group HbA1C (P0.05).2.T1DM group, the course of disease, blood glucose fluctuation parameters in T1DM group were 9.2 + 6 years duration, HbA1C:9.44 + 2.41%, the average blood glucose (MBG): 9.43 + 2.44mmol/l, average blood glucose fluctuation (MAGE): 6.20 + 2.24mmol/l, daytime blood glucose average absolute difference (MODD): 3.87 + 1.58mmol/l. Standard deviation of blood glucose (SDBG): 2.39 + 0.85mmol/l, low glycemic index (LBGI): 2.50 + 2.44, the percentage of blood glucose less than 3.9mmol/l (glu70): 3.37 + 3.88%.3. between the two groups of cognitive function and hippocampal metabolites, brain functional connectivity than than in the T1DM group compared with the normal control group, DSST, RAVLT (1-5) test total the ROCF copy is below 甯稿鐓х粍(P0.05);宸︿晶娴烽┈NAA/Cr浣庝簬瀵圭収缁，
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