Han Ziping, Li Lingzhi, Tao Zhen, Wang Rongliang, Zhao Haiping, Zheng Yangmin, Yang Zhenhong, Zhong Liyuan, Fan Junfen, Luo Yumin
Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.
Front Pharmacol. 2022 Oct 6;13:1003806. doi: 10.3389/fphar.2022.1003806. eCollection 2022.
There's no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0-1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ -0.336 (OR = 2.862 [1.029-7.958], = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65-8.71], = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54-71.49], = 0.016). The noncoding RNA score ≥ -0.336 (OR = 5.250 [1.096-25.135], = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.
没有证据表明静脉注射重组组织型纤溶酶原激活剂（rtPA）前非编码RNA水平与急性缺血性卒中（AIS）的预后之间存在关联。2018年至2019年在卒中中心招募了145例接受rtPA治疗的AIS患者，本研究纳入了103例患者。在rtPA治疗前检测了AIS患者循环中性粒细胞中的一组非编码RNA（miRNA - 23a、miRNA - 193a、miRNA - 128、miRNA - 99a、miRNA - let - 7a、miRNA - 494、miRNA - 424和lncRNA H19）。终点指标包括3个月时的良好预后（改良Rankin量表评分[mRS]0 - 1）或不良预后（mRS>1）以及rtPA治疗后有症状性脑出血（sICH）。在103名参与者循环中性粒细胞中检测到的8种非编码RNA中，miRNA - 23a水平与入院时的卒中严重程度以及rtPA治疗后24小时的症状进展相关。筛选出由miRNA - 23a、miRNA - 99a和lncRNA H19组成的非编码RNA评分，以预测rtPA治疗后3个月的功能预后和sICH的发生率。在逻辑回归分析中，非编码RNA评分≥ - 0.336（OR = 2.862[1.029 - 7.958]，P = 0.044）是调整临床变量后3个月不良预后的独立预测因子，将非编码RNA评分添加到临床模型中可提高辨别力（IDI% = 4.68[0.65 - 8.71]，P = 0.020）以及净重新分类（NRI% = 33.04[0.54 - 71.49]，P = 0.016）。非编码RNA评分≥ - 0.336（OR = 5.250[1.096 - 25.135]，P = 0.038）也可独立预测sICH，将非编码RNA评分添加到临床变量中同样可提高辨别力和重新分类。非编码RNA评分还与rtPA治疗后7天的梗死体积和症状改善相关。总之，较高的中性粒细胞非编码RNA评分可为识别rtPA治疗后预后较差的AIS患者提供预测价值。miRNA - 23a、miRNA - 99a和lncRNA H19在AIS后溶栓中的作用值得进一步研究。
