关于替奈普酶治疗缺血性脑卒中：现阶段研究进展及精准治疗策略

Tenecteplase for Ischemic Stroke: Current Research Progress and Precision Treatment Strategies

摘要: 急性缺血性脑卒中溶栓治疗因第三代药物替奈普酶(TNK)取得重要进展。相较于传统阿替普酶(ALT)，TNK通过基因工程改良实现三大优势：纤维蛋白特异性增强14倍、抗PAI-1能力提升80倍及半衰期延长至22分钟，支持单次静脉推注。临床试验证实，0.25 mg/kg剂量TNK在大血管闭塞患者中再通率提升至32.6%，桥接取栓时再通率显著优于ALT (OR = 2.10)。针对80岁以上患者，0.4 mg/kg剂量TNK疗效与ALT相当(mRS 0~1达成率43.1% vs 39.9%)，且安全性良好。影像指导下的个体化治疗可将溶栓时间窗扩展至24小时。当前证据显示TNK在特殊人群及桥接治疗中具显著优势，但需结合血栓组学等研究优化剂量策略。未来应建立血栓表型导向的精准给药模型，推动溶栓治疗个体化革新。

Abstract: Thrombolytic therapy for acute ischemic stroke (AIS) has advanced significantly with the third-generation agent tenecteplase (TNK). Compared to alteplase (ALT), TNK offers three pharmacological advantages through genetic engineering: 14-fold higher fibrin specificity, 80-fold stronger resistance to PAI-1, and an extended 22-minute half-life, enabling single intravenous bolus administration. Clinical trials demonstrate that TNK at 0.25 mg/kg achieves optimal efficacy-safety balance, increasing recanalization rates to 32.6% in large vessel occlusion (LVO) patients (CHABLIS-T trial) and showing superior early recanalization versus ALT during bridging thrombectomy (OR = 2.10). For elderly patients (≥80 years), 0.4 mg/kg TNK exhibits comparable efficacy (mRS 0~1 rates: 43.1% vs 39.9%) and safety to ALT. Perfusion imaging-guided individualized strategies extend the thrombolytic time window to 24 hours (TRACE III trial). Current evidence highlights TNK's advantages in LVO subgroups, bridging therapy, and special populations, though dose optimization requires thrombus omics and genomic studies. Future research should focus on thrombus phenotype-driven precision dosing models to advance personalized thrombolytic therapy.