不同严重程度阿尔茨海默病患者血清miR-128,miR-223表达水平变化与炎症反应及认知功能的相关性分析

The correlation betweenthe expression of serum miR-128 and miR-223 and inflammatory response and cognition in patients with different severity of Alzheimer’s disease

目的探讨不同严重程度阿尔茨海默病(Alzheimer’s disease, AD)患者血清微小RNA(MicroRNA,miR)-128,miR-223表达水平变化与炎症反应及认知功能的相关性。方法选择2018年6月-2020年1月本院收治的200例AD患者(AD组),根据临床痴呆评定量表(Clinical dementia rating scale, CDR)评分将AD患者分为轻度组(CDR评分1分,66例)、中度组(CDR评分2分,83例)、重度组(CDR评分3,51例)3个亚组,另选择207例体检健康志愿者为对照组;采用简易智能精神状态检查量表(Mini-mental state examination, MMSE)评估AD患者认知功能;检测所有受试者血清miR-128,miR-223表达水平;检测AD患者血清白介素-6(Interleukin-6,IL-6)、白介素-1β(Interleukin-1,IL-1β)、肿瘤坏死因子-α(Tumor necrosis factor-,TNF-α)、C反应蛋白(C-reactive protein, CRP)水平;分析血清miR-128,miR-223表达水平与TNF-α,IL-1β,IL-6,CRP水平、MMSE总分的相关性。结果 AD组血清miR-128表达水平高于对照组(P<0.05),miR-223表达水平低于对照组(P<0.05)。重度组血清miR-128表达水平、TNF-α,IL-1β,IL-6,CRP水平高于中度和轻度组(P<0.05),且中度组高于轻度组(P<0.05);重度组血清miR-223表达水平、MMSE总分低于中度和轻度组(P<0.05),且中度组低于轻度组(P<0.05)。miR-128表达水平与TNF-α,IL-1β,IL-6,CRP呈正相关(r≥0.496,P<0.05),与MMSE总分呈负相关(r=-0.571,P<0.05);miR-223表达水平与TNF-α,IL-1β,IL-6,CRP呈负相关(r≤-0.572,P<0.05),与MMSE总分呈正相关(r=0.531,P<0.05)。结论 AD患者血清miR-128表达水平上调,miR-223表达水平下调,两者异常变化可能诱导炎症反应,进而参与AD患者认知功能损伤过程。

Objective To investigate the correlation between the expression of serum microRNA(miR)-128 and miR-223 and inflammatory factors andcognitive functionin patientswith different severity of Alzheimer’s disease(AD). Methods 200 cases of patients with AD(AD group) who were admitted to our hospital from June 2018 to January 2020 were selected.According to the clinical dementia rating scale(CDR) score, the patients with AD were divided into 3 subgroups, includingmild group(CDR score=1, 66 cases), moderate group(CDR score=2, 83 cases), severe group(CDR score=3, 51 cases), and 207 volunteers were as control group. The cognitive function of patients with AD was evaluated by mini mental state examination(MMSE).The expression of serum miR-128 and miR-223 were detectedin all subjects, and the levels of serum interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and C-reactive protein(CRP) inpatients with AD were also detected. The correlation between theexpression of miR-128 and miR-223 and the levels of serum TNF-α, IL-1β, IL-6, CRP, MMSEscoreswas analyzed. Results Theexpression of serum miR-128 in AD group was higher than that in control group(P<0.05), while the miR-223 expression in AD groupwas lower than that in control group(P<0.05). The expression of serum miR-128, TNF-α, IL-1β, IL-6, CRP levelsin severe group were higher than those in moderate and mild groups(P<0.05), and those inthe moderate group was higher than the mild group(P<0.05). The expression of miR-223 and MMSE scores in severe group were lower than those in the moderate and mild groups(P<0.05), and those inthe moderate group was lower than the mild group(P<0.05). The miR-128 expression was positively correlated with TNF-α, IL-1β, IL-6 and CRP(r≥0.496, P<0.05), and negatively correlated with MMSE score(r =-0.571, P<0.05). The miR-223 expression was negatively correlated with TNF-α, IL-1β, IL-6 and CRP(r≤-0.572, P<0.05), and positively correlated with MMSE score(r=0.531, P<0.05). Conclusion The serum miR-128 expression was up-regulated, and miR-223 expression was down-regulated in patients with AD, which may induce inflammatory response and then participate in the process of cognitive impairment in patients with AD.