Department of Neurology, The Second Hospital of Tianjin medical University, Tianjin, China.
Tianjin Institute of Urology, Tianjin, China.
J Physiol Pharmacol. 2022 Feb;73(1). doi: 10.26402/jpp.2022.1.11. Epub 2022 Jul 4.
To investigate the relationship between plasma microRNA-223 expression and platelet reactivity in patients with acute ischemic stroke (AIS) and to evaluate its predictive value in clopidogrel resistance or high on-treatment platelet reactivity (HTPR). A total of 120 patients with acute ischemic stroke were screened in this study, and 60 patients were included in the acute ischemic stroke group according to the inclusion criteria and platelet reactivity after clopidogrel treatment. control group was 60 non-ischemic stroke patients hospitalized. The levels of phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and adenosine diphosphate-induced platelet aggregation (ADP-PAg) in platelets were detected by flow cytometry. The expression level of plasma microRNA-223 was detected before and after clopidogrel treatment using quantitative real-time polymerase chain reaction (PcR). The AIS group was then divided into the clopidogrel non-HTPR and the clopidogrel HTPR groups based on the relative inhibition rate. We found that: 1) the VASP platelet reactivity index (PRI) was positively correlated with ADP-PAg; 2) before administration, the plasma microRNA-223 expression level and VASP-PRI were higher in the AIS group than in the control group; 3) after administration, the expression level of microRNA-223 was negatively correlated with VASP-PRI; 4) before and after treatment, the plasma microRNA-223 expression level in the clopidogrel HTPR group was lower than in the non-AIS patients; 5) before treatment, there was an interaction between the expression level of microRNA-223 in the plasma and the cYP2c19 loss-of-function (LOF) allele. The study showed that decreased plasma microRNA-223 expression levels in AIS patients indicate an increased risk of clopidogrel HTPR. carrying cYP2c19 LOF alleles may result in the microRNA-223 expression being more distinct. The combined detection of plasma microRNA-223 and cYP2c19 gene polymorphisms may be effective in predicting the occurrence of clopidogrel HTPR in patients with AIS.
探讨急性缺血性脑卒中（AIS）患者血浆微小 RNA-223 表达与血小板反应性的关系，并评估其对氯吡格雷抵抗或治疗中血小板高反应性（HTPR）的预测价值。
本研究筛选了 120 例急性缺血性脑卒中患者，根据纳入标准和氯吡格雷治疗后血小板反应性，将 60 例患者纳入急性缺血性脑卒中组，对照组为 60 例非缺血性脑卒中住院患者。采用流式细胞术检测血小板磷酸化血管扩张刺激磷蛋白（VASP）和二磷酸腺苷诱导的血小板聚集（ADP-PAg）水平。采用实时定量聚合酶链反应（PCR）检测氯吡格雷治疗前后血浆微小 RNA-223 的表达水平。根据相对抑制率将 AIS 组分为氯吡格雷非 HTPR 组和氯吡格雷 HTPR 组。
1）VASP 血小板反应性指数（PRI）与 ADP-PAg 呈正相关；2）治疗前，AIS 组血浆微小 RNA-223 表达水平和 VASP-PRI 均高于对照组；3）治疗后，微小 RNA-223 表达水平与 VASP-PRI 呈负相关；4）治疗前后，氯吡格雷 HTPR 组患者血浆微小 RNA-223 表达水平均低于非 AIS 患者；5）治疗前，血浆微小 RNA-223 表达水平与 cYP2c19 功能丧失（LOF）等位基因之间存在交互作用。
AIS 患者血浆微小 RNA-223 表达水平降低提示氯吡格雷 HTPR 风险增加。携带 cYP2c19 LOF 等位基因可能导致微小 RNA-223 表达更为显著。联合检测血浆微小 RNA-223 和 cYP2c19 基因多态性可能有助于预测 AIS 患者氯吡格雷 HTPR 的发生。
