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基于血小板激活因子拮抗剂的强化抗血小板策略治疗急性缺血性脑卒中:倾向评分匹配与网络药理学分析。

Platelet-activating factor antagonist-based intensive antiplatelet strategy in acute ischemic stroke: A propensity score matched with network pharmacology analysis.

机构信息

Department of Neurology, First People's Hospital of Zhaoqing, Zhaoqing, People's Republic of China.

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

出版信息

CNS Neurosci Ther. 2023 Dec;29(12):4082-4092. doi: 10.1111/cns.14331. Epub 2023 Jul 12.

Abstract

BACKGROUND

Diterpene ginkgolides meglumine injection (DGMI) is a platelet-activating factor receptor (PAFR) antagonist that can be used to treat acute ischemic stroke (AIS). This study evaluated the efficacy and safety of an intensive antiplatelet strategy based on PAFR antagonists and explored the underlying mechanisms of PAFR antagonists in AIS treatment.

METHODS

This is a retrospective study applying propensity score methods to match AIS patients treated with DGMI to nontreated patients. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 90 days. The safety outcome was bleeding risk. We used McNemar test to compare the efficacy outcome. Subsequently, the network pharmacology analysis was performed.

RESULTS

161 AIS patients treated with DGMI in the study were matched with 161 untreated patients. Compared with untreated patients, DGMI-treated patients had a significantly higher rate of mRS ranking 0-2 at 90 days (82.0% vs. 75.8%, p < 0.001), without increased risk of bleeding. The gene enrichment analysis showed that the overlap genes of DGMI targeted and AIS-related enriched in thrombosis and inflammatory-related signaling pathways.

CONCLUSIONS

An intensive antiplatelet strategy of DGMI plus traditional antiplatelet agents is effective in treating AIS and may work by mediating post-stroke inflammation and thrombosis.

摘要

背景

银杏二萜内酯葡胺注射液(DGMI)是一种血小板激活因子受体(PAFR)拮抗剂,可用于治疗急性缺血性脑卒中(AIS)。本研究评估了基于 PAFR 拮抗剂的强化抗血小板策略的疗效和安全性,并探讨了 PAFR 拮抗剂在 AIS 治疗中的潜在机制。

方法

这是一项回顾性研究,采用倾向评分匹配方法将接受 DGMI 治疗的 AIS 患者与未接受治疗的患者进行匹配。主要结局为 90 天时的功能独立性(改良 Rankin 量表 [mRS] 0-2)。安全性结局为出血风险。我们使用 McNemar 检验比较疗效结局。随后进行网络药理学分析。

结果

研究中 161 例接受 DGMI 治疗的 AIS 患者与 161 例未接受治疗的患者进行了匹配。与未接受治疗的患者相比,DGMI 治疗组在 90 天时 mRS 评分 0-2 的比例显著更高(82.0% vs. 75.8%,p<0.001),且出血风险并未增加。基因富集分析表明,DGMI 靶向的重叠基因与 AIS 相关的基因在血栓形成和炎症相关信号通路中富集。

结论

DGMI 联合传统抗血小板药物的强化抗血小板策略治疗 AIS 有效,可能通过调节卒中后炎症和血栓形成发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e31/10651968/6a769a88c8f8/CNS-29-4082-g003.jpg

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