作者：高倩，王建宇，孟伟建，李静，崔永健，魏琰

单位：

053000河北省衡水市人民医院 哈励逊国际和平医院神经内二科

Units：

Two Department of Neurology, Hengshui People's Hospital/Harrison International Peace Hospital, Hengshui 053000, China

关键词：

脑梗死；微小RNA-145；程序性细胞死亡因子4；诊断

Keywords：

Brain infarction; MicroRNA-145; Programmed cell death 4; Diagnosis

CLC：

R 743.33

DOI：

10.12114/j.issn.1008-5971.2022.00.033

Funds：

河北省卫生厅科研基金项目（20181592）

摘要：

背景　急性脑梗死（ACI）发病率、致残率均较高，威胁患者健康，故早期诊断ACI对于针对性治疗 方案的制定及患者预后的改善具有积极意义。微小RNA-145（miR-145）靶向下调程序性细胞死亡因子4（PDCD4） 水平可缓解ACI引起的炎性反应，二者可能与ACI的发生有关。目的　分析ACI患者血清miR-145、PDCD4 mRNA水平 变化及诊断价值。方法　选择2019年1月至2020年6月衡水市人民医院神经内科收治的ACI患者185例为ACI组。根据入 院时美国国立卫生研究院卒中量表（NIHSS）评分将ACI患者进一步分为轻度损伤亚组（NIHSS评分≤15分，72例）、 中度损伤亚组（NIHSS评分为16~29分，64例）、重度损伤亚组（NIHSS评分≥30分，49例）。根据ACI患者脑梗死 体积大小，将其进一步分为小体积亚组（脑梗死体积＜5 cm3，69例）、中等体积亚组（脑梗死体积为5~10 cm3，62 例）、大体积亚组（脑梗死体积＞10 cm3，54例）。同期选择在本院体检的健康者150例为对照组。收集所有受试者 一般资料，并检测其血清miR-145、PDCD4 mRNA水平。采用Pearson相关分析探讨ACI患者血清miR-145水平与血清 PDCD4 mRNA水平间的相关性；采用多因素Logistic回归分析探讨ACI的影响因素；采用受试者工作特征（ROC）曲线 分析胱抑素C及血清miR-145、PDCD4 mRNA水平对ACI的诊断价值。结果　ACI组有高血压史者所占比例、收缩压、 舒张压、低密度脂蛋白胆固醇（LDL-C）、同型半胱氨酸、胱抑素C高于对照组（P ＜0.05）。ACI组血清miR-145水 平低于对照组，血清PDCD4 mRNA水平高于对照组（P ＜0.05）。中度损伤亚组、重度损伤亚组血清miR-145水平低于 轻度损伤亚组，血清PDCD4 mRNA水平高于轻度损伤亚组（P ＜0.05）；重度损伤亚组血清miR-145水平低于中度损伤 亚组，血清PDCD4 mRNA水平高于中度损伤亚组（P ＜0.05）。中等体积亚组、大体积亚组血清miR-145水平低于小 体积亚组，血清PDCD4 mRNA水平高于小体积亚组（P ＜0.05）；大体积亚组血清miR-145水平低于中等体积亚组， 血清PDCD4 mRNA水平高于中等体积亚组（P ＜0.05）。Pearson相关分析结果显示，ACI患者血清miR-145水平与血清 PDCD4 mRNA水平呈负相关（r =-0.327，P ＜0.001）。多因素Logistic回归分析结果显示，胱抑素C〔OR =1.869，95%CI （1.181，2.957）〕及血清miR-145〔OR =2.008，95%CI （1.315，3.066）〕、PDCD4 mRNA水平〔OR =1.843，95%CI （1.308，2.597）〕是ACI的影响因素（P ＜0.05）。ROC曲线分析结果显示，血清miR-145水平联合血清PDCD4 mRNA 水平诊断ACI的曲线下面积（AUC）大于胱抑素C、血清miR-145水平、血清PDCD4 mRNA水平单独诊断ACI的AUC（P ＜0.05）。结论　ACI患者血清miR-145水平下降、血清PDCD4 mRNA水平升高，其均与患者神经功能缺损程度和脑梗 死体积有关，且二者联合对ACI具有较高的诊断价值，其可能是临床上早期诊断ACI的潜在生物标志物。

Abstract：

Background　The incidence rate and disability rate of acute cerebral infarction (ACI) are high, threatening the health of patients. Early diagnosis of ACI are of positive significance for the formulation of targeted treatment andthe improvement of prognosis. Targeted downregulation of programmed cell death 4 (PDCD4) levels by microRNA-145 (miR- 145) can alleviate the inflammatory response caused by ACI, and the two may be related to the occurrence of ACI. Objective　 To investigate the changes and diagnostic value of serum miR-145 and PDCD4 mRNA in patients with ACI. Methods　A total of 185 ACI patients admitted to the Department of Neurology of Hengshui People's Hospital from January 2019 to June 2020 were selected as ACI group. According to the National Institutes of Health Stroke Scale (NIHSS) score at admission, ACI patients were further divided into mild injury subgroup (NIHSS score ≤ 15, 72 cases) , moderate injury subgroup (NIHSS score 16~29, 64 cases) and severe injury subgroup (NIHSS score ≥ 30, 49 cases) . According to the size of cerebral infarction, ACI patients were further divided into small volume subgroup (cerebral infarction volume 10 cm3, 54 cases) . In the same period, 150 healthy persons who came to our hospital for physical examination were selected as the control group. The general data of all subjects were collected, and the levels of serum miR-145 and PDCD4 mRNA were detected. Pearson correlation analysis was used to explore the correlation between serum miR-145 level and serum PDCD4 mRNA level in patients with ACI; multivariate Logistic regression analysis was used to explore the influencing factors of ACI; the diagnostic value of cystatin C, serum miR- 145 and PDCD4 mRNA levels in ACI was analyzed by receiver operating characteristic (ROC) curve. Results　The proportion of patients with hypertension history, systolic blood pressure, diastolic blood pressure, low density lipoprotein cholesterol (LDL-C) , homocysteine and cystatin C in ACI group were significantly higher than those in the control group (P < 0.05) . The level of serum miR-145 in ACI group was lower than that in control group, and the level of serum PDCD4 mRNA was higher than that in control group (P < 0.05) . The level of serum miR-145 in moderate injury subgroup and severe injury subgroup was lower than that in mild injury subgroup, and the level of serum PDCD4 mRNA was higher than that in mild injury subgroup (P < 0.05) ; the level of serum miR-145 in severe injury subgroup was lower than that in moderate injury subgroup, and the level of serum PDCD4 mRNA was higher than that in moderate injury subgroup (P < 0.05) . The level of serum miR-145 in medium volume subgroup and large volume subgroup was lower than that in small volume subgroup, and the level of serum PDCD4 mRNA was higher than that in small volume subgroup (P < 0.05) ; the level of serum miR-145 in large volume subgroup was lower than that in medium volume subgroup, and the level of serum PDCD4 mRNA was higher than that in medium volume subgroup (P < 0.05) . Pearson correlation analysis showed that there was a negative correlation between serum miR-145 level and serum PDCD4 mRNA level in patients with ACI (r =-0.327, P < 0.001) . Multivariate Logistic regression analysis showed that cystatin C [OR =1.869, 95%CI (1.181, 2.957) ] , serum miR-145 level [OR =2.008, 95%CI (1.315, 3.066) ] and serum PDCD4 mRNA level [OR =1.843, 95%CI (1.308, 2.597) ] were the influencing factors of ACI (P < 0.05) . ROC curve analysis showed that the area under curve (AUC) of serum miR-145 level combined with serum PDCD4 mRNA level in the diagnosis of ACI was greater than that of cystatin C, serum miR-145 level and serum PDCD4 mRNA level alone (P < 0.05) . Conclusion　The level of serum miR-145 decreased and the level of serum PDCD4 mRNA increased in ACI patients, both of which are related to the degree of neurological deficit and the size of cerebral infarction, and the combination of the two has a high diagnostic value for ACI, which may be a potential biomarker for early diagnosis of ACI in clinical practice.

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