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血清miR-340-5p和APPL1水平与老年阿尔茨海默病患者炎症反应与认知功能的相关性 被引量:6

Correlation of serum miR-340-5p and APPL1 levels with inflammatory response and cognitive function in elderly patients with Alzheimer’s disease
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摘要 目的探讨血清微小RNA(miR)-340-5p、磷酸酪氨酸衔接蛋白1(APPL1)水平与老年阿尔茨海默病(AD)患者炎症反应、认知功能的相关性。方法选择2019年1月-2021年12月国药葛洲坝中心医院110例老年AD患者(AD组)和110名健康体检者(NC组)。AD组患者依据临床痴呆评定量表评分分为轻度AD组、中度AD组、重度AD组,采用简易智能精神状态检查量表(MMSE)评估认知功能损伤程度并分为轻度认知功能障碍组、中度认知功能障碍组、重度认知功能障碍组。比较各组超敏C-反应蛋白(hs-CRP)、miR-340-5p、APPL1、白细胞介素-1β(IL-1β)、IL-6水平,Pearson相关性分析血清miR-340-5p、APPL1与炎性因子以及认知功能评分的相关性。受试者工作特征(ROC)曲线分析血清miR-340-5p、APPL1水平对AD的诊断价值。结果AD组血清miR-340-5p表达水平低于NC组,APPL1表达水平高于NC组,差异有统计学意义(t=12.473、10.898,P均<0.05)。轻度AD组、中度AD组、重度AD组血清miR-340-5p表达水平依次降低,APPL1表达水平依次增加,差异有统计学意义(F=14.202、15.477,P均<0.05)。轻度认知功能障碍组、中度认知功能障碍组及重度认知功能障碍组血清miR-340-5p表达水平依次降低,APPL1表达水平依次增加,差异有统计学意义(F=18.081、9.548,P均<0.05)。AD组MMSE评分显著低于NC组,IL-1β、IL-6、hs-CRP水平高于NC组,差异有统计学意义(t=39.654、18.064、24.683、48.218,P均<0.05)。轻度AD组、中度AD组、重度AD组MMSE评分依次降低,而hs-CRP、IL-1β、IL-6水平依次增加,差异有统计学意义(F=39.863、153.382、86.058、44.757,P均<0.05)。相关性分析显示,AD组血清miR-340-5p与MMSE评分成正相关,与IL-1β、IL-6、APPL1、hs-CRP存在负相关(r=0.615、-0.469、-0.504、-0.658、-0.427,P均<0.05);而APPL1与MMSE评分成负相关,与hs-CRP、IL-1β、IL-6水平成正相关(r=-0.637、0.490、0.549、0.458,P均<0.05)。ROC分析显示,miR-340-5p对AD诊断的曲线下面积(AUC)为0.858(95%CI:0.809~0.907),APPL1对AD诊断的AUC为0.822(95%CI:0.768~0.877),APPL1联合miR-340-5p诊断AD的AUC为0.927(95%CI:0.893~0.961)。结论miR-340-5p在AD患者血清中表达降低,APPL1表达升高,均与病情严重程度、炎症反应及认知功能损伤相关,且对AD有一定诊断价值。 Objective To investigate the correlation of serum microRNA(miR)-340-5p and adaptor protein,phosphotyrosineinteraction,PH domain and leucine zipper containing 1(APPL1)levels with inflammatory response and cognitive functionin elderly patients with Alzheimer’s disease(AD).MethodsFrom January 2019 to December 2021,110 elderly ADpatients(AD group)and 110 healthy people(NC group)in our hospital were selected.The patients in AD group weredivided into mild AD group,moderate AD group and severe AD group according to the score of clinical dementia assessmentscale.The degree of cognitive function impairment was assessed by mini-mental state examination(MMSE)and divided intomild cognitive impairment group,moderate cognitive impairment group and severe cognitive impairment group.Comparisonof the levels of high sensitivity C-reactive protein(hs-CRP),mi R-340-5p,APPL1,interleukin(IL)-1βand IL-6 in eachgroup.Pearson correlation analysis of miR-340-5p and APPL1 levels with inflammatory factors and cognitive function scores.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum miR-340-5p andAPPL1 levels in AD.ResultsThe expression level of mi R-340-5p in AD group was lower than that in NC group,and theexpression level of APPL1 was higher than that in NC group,and the differences were statistically significant(t=12.473,10.898,all P<0.05).The expression levels of serum mi R-340-5p in mild AD group,moderate AD group and severe ADgroup decreased in turn,while the expression level of APPL1 increased in turn,and the differences were statisticallysignificant(F=14.202,15.477,all P<0.05).The expression levels of serum mi R-340-5p in the mild cognitive impairmentgroup,the moderate cognitive impairment group and the severe cognitive impairment group decreased in turn,while theexpression levels of APPL1 increased in turn,and the differences were statistically significant(F=18.081,9.548,all P<0.05).The MMSE score of AD group was significantly lower than that of NC group,and the levels of IL-1β,IL-6,and hs-CRPwere higher than those of NC group,and the differences were statistically significant(t=39.654,18.064,24.683,48.218,all P<0.05).The MMSE scores of mild AD group,moderate AD group,and severe AD group decreased in turn,while thelevels of hs-CRP,IL-1β,and IL-6 increased in turn,and the differences were statistically significant(F=39.863,153.382,86.058,44.757,all P<0.05).Correlation analysis showed that serum mi R-340-5p in AD group was positively correlatedwith MMSE score,and negatively correlated with IL-1β,IL-6,APPL1,hs-CRP(r=0.615,-0.469,-0.504,-0.658,-0.427,all P<0.05);APPL1 was negatively correlated with MMSE scores,and positively correlated with hs-CRP,IL-1β,and IL-6levels(r=-0.637,0.490,0.549,0.458,all P<0.05).ROC analysis showed that the area under the curve(AUC)of mi R-340-5p for AD diagnosis was 0.858(95%CI:0.809-0.907),the AUC of APPL1 for AD diagnosis was 0.822(95%CI:0.768-0.877),and the AUC of APPL1 combined with mi R-340-5p in the diagnosis of AD was 0.927(95%CI:0.893-0.961).ConclusionThe expression of mi R-340-5p was decreased in the serum of AD patients,and the expression ofAPPL1 was increased,which were related to the severity of the disease,inflammatory response and cognitive impairment,and had certain diagnostic value for AD.
作者 邓天玲 段爱琴 曾敏玲 张爽 DENG Tian-ling;DUAN Ai-qin;ZENG Min-ling;ZHANG Shuang(Department of Neurology,Sinopharm Gezhouba Central Hospital,Yichang,Hubei 443000,China)
出处 《热带医学杂志》 CAS 2022年第11期1551-1556,共6页 Journal of Tropical Medicine
基金 湖北省卫生健康委员会联合基金(WJ2019H570)
关键词 阿尔茨海默病 微小RNA-340-5p 磷酸酪氨酸衔接蛋白1 炎症反应 认知功能 Alzheimer’s disease microRNA-340-5p APPL1 Inflammatory response Cognitive function
作者简介 邓天玲(1976-),女,本科,副主任医师,从事脑血管病,神经系统变性疾病方面研究工作;通信作者:段爱琴,E-mail:407417177@qq.com
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