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血压对急性缺血性脑卒中静脉 rt-PA 溶栓患者早期神经功能恶化的影响可能通过氧化应激诱导的血脑屏障破坏和 AQP4 上调介导。

Effect of blood pressure on early neurological deterioration of acute ischemic stroke patients with intravenous rt-PA thrombolysis may be mediated through oxidative stress induced blood-brain barrier disruption and AQP4 upregulation.

机构信息

Department of Geriatric Medicine, the Second People's Hospital of Yibin, Yibin, China.

Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104997. doi: 10.1016/j.jstrokecerebrovasdis.2020.104997. Epub 2020 Jun 13.

DOI:10.1016/j.jstrokecerebrovasdis.2020.104997
PMID:32689627
Abstract

OBJECTIVE

To study association between blood pressure (BP) and development of early neurological deterioration (END) in acute ischemic stroke patients with intravenous rt-PA thrombolysis and its possible mechanism.

METHODS

We prospectively collected data of acute ischemic stroke patients with intravenous rt-PA thrombolysis from March 2015 to June 2019. The collected data include general, clinical data and laboratory test. Moreover, serum levels or activity of malondialdehyde (MDA), superoxide dismutase (SOD), matrix metalloproteinase-9 (MMP-9), occludin(OCLN), ZO-1 and aquaporin 4(AQP-4) were determined.

RESULTS

A total of 357 acute ischemic stroke patients received intravenous rt-PA thrombolysis and 16 cases were eventually excluded. Finally, 341 patients were eligible in this study and 65 patients (19.06%) experienced END. Mean systolic blood pressure (SBP) within 24 h, serum levels or activity of MDA, SOD, MMP-9, ZO-1, OCLN, AQP-4 at 24 h after thrombolysis were the independent predictors for END in the total and hypertension population using multivariate logistic regression analysis, and mean SBP within 24 h was the best predictor for END. Receiver operating characteristic (ROC) analysis found that cutoff mean SBP for END was 148.16 mmHg, and sensitivity was 85.6%. The best target SBP level is 140ཞ149 mmHg. Further, spearman correlation tests indicated that BP levels were directly proportional to serum levels or activity of MDA, MMP-9, ZO-1, OCLN, AQP-4 at 24 h after thrombolysis and neurological deterioration severity.

CONCLUSIONS

END frequently occurs after thrombolysis, and the best predictor of END is SBP which may be mediated through oxidative stress induced blood-brain barrier disruption and AQP4 upregulation.

摘要

目的

研究急性缺血性脑卒中患者静脉 rt-PA 溶栓后血压(BP)与早期神经功能恶化(END)的相关性及其可能的机制。

方法

前瞻性收集 2015 年 3 月至 2019 年 6 月接受静脉 rt-PA 溶栓治疗的急性缺血性脑卒中患者数据。收集的数据包括一般、临床和实验室检查。此外,还测定了丙二醛(MDA)、超氧化物歧化酶(SOD)、基质金属蛋白酶-9(MMP-9)、occludin(OCLN)、紧密连接蛋白-1(ZO-1)和水通道蛋白 4(AQP-4)的血清水平或活性。

结果

共 357 例急性缺血性脑卒中患者接受静脉 rt-PA 溶栓治疗,最终排除 16 例,最终纳入本研究 341 例患者,其中 65 例(19.06%)发生 END。多变量 logistic 回归分析显示,溶栓后 24 小时内平均收缩压(SBP)、MDA、SOD、MMP-9、ZO-1、OCLN、AQP-4 血清水平或活性是全人群和高血压人群发生 END 的独立预测因素,溶栓后 24 小时内平均 SBP 是预测 END 的最佳指标。受试者工作特征(ROC)分析发现,预测 END 的平均 SBP 截断值为 148.16mmHg,敏感性为 85.6%。最佳目标 SBP 水平为 140ཞ149mmHg。进一步的 Spearman 相关分析表明,BP 水平与溶栓后 24 小时内 MDA、MMP-9、ZO-1、OCLN、AQP-4 血清水平或活性以及神经功能恶化程度呈正相关。

结论

溶栓后 END 发生率较高,最佳预测因子是 SBP,可能通过氧化应激引起血脑屏障破坏和 AQP4 上调。

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