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亚低温联合远程缺血后处理和溶栓治疗对急性缺血性脑卒中患者的脑保护作用。

Brain Protection Effects of Mild Hypothermia Combined with Distant Ischemic Postconditioning and Thrombolysis in Patients with Acute Ischemic Stroke.

机构信息

Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin, China.

Department of Pediatrics, Qingdao Huangdao District Central Hospital, Qingdao, China.

出版信息

Ther Hypothermia Temp Manag. 2024 Sep;14(3):172-178. doi: 10.1089/ther.2023.0043. Epub 2023 Sep 4.

Abstract

To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection,  = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline,  = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group ( < 0.05). While the SOD in the experimental group was significantly higher than in the control group ( < 0.05), the NIHSS scores decreased within groups (all  < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%,  < 0.05) and no significant differences were observed in the safety indices between the two groups (all  > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.

摘要

评估亚低温和远程缺血后处理(RIPC)对接受重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗的急性缺血性脑卒中(AIS)患者的有效性和分子机制。本前瞻性研究共纳入 58 例接受重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗的 AIS 患者。参与者被随机分配到实验组(rt-PA 静脉溶栓+亚低温冰帽+远程缺血性脑保护,n=30)和对照组(rt-PA 静脉溶栓+0.9%生理盐水,n=28)。在连续 14 天内,对双侧上肢动脉进行 RIPC,两次间隔 2 分钟。依次进行 5 个周期的缺血-再灌注(分别为 2-2、3-3、4-4、5-5、5-0 分钟)。在治疗后不同时间点评估国立卫生研究院卒中量表(NIHSS)评分、脑梗死体积、血清超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素-1β、肿瘤坏死因子-α、核因子-κB(NF-κB)和核苷酸结合寡聚化结构域样受体 3(NLRP3)水平。同样,比较两组患者 90 天改良 Rankin 量表(mRS)评分。治疗后,实验组 NIHSS 评分、MDA、NF-κB 和 NLRP3 水平明显低于对照组(均 P<0.05),SOD 水平明显高于对照组(均 P<0.05),两组 NIHSS 评分均较治疗前降低(均 P<0.05)。实验组 90 天 mRS 评分(0-2 分)明显高于对照组(73.33% vs. 53.57%,P<0.05),两组安全性指标差异无统计学意义(均 P>0.05)。本研究表明,亚低温联合 RIPC 对脑保护具有积极作用,可显著降低氧化应激及相关炎症反应的爆发。临床试验注册号为 ChiCTR2300073136。

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