Ma Guodong, Pan Zirong, Kong Linglei, Du Guanhua
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Centre for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Centre for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int Immunopharmacol. 2021 Jan;90:107216. doi: 10.1016/j.intimp.2020.107216. Epub 2020 Dec 6.
Hemorrhagic transformation (HT) is a common and serious complication following ischemic stroke, especially after tissue plasminogen activator (t-PA) thrombolysis, which is associated with increased mortality and disability. Due to the unknown mechanisms and targets of HT, there are no effective therapeutic drugs to decrease the incidence of HT. In recent years, many studies have found that neuroinflammation is closely related to the occurrence and development of HT after t-PA thrombolysis, including glial cell activation in the brain, peripheral inflammatory cell infiltration and the release of inflammatory factors, involving inflammation-related targets such as NF-κB, MAPK, HMGB1, TLR4 and NLRP3. Some drugs with anti-inflammatory activity have been shown to protect the BBB and reduce the risk of HT in preclinical experiments and clinical trials, including minocycline, fingolimod, tacrolimus, statins and some natural products. In addition, the changes in MMP-9, VAP-1, NLR, sICAM-1 and other inflammatory factors are closely related to the occurrence of HT, which may be potential biomarkers for the diagnosis and prognosis of HT. In this review, we summarize the potential inflammation-related mechanisms, targets, therapeutic drugs, and biomarkers associated with HT after t-PA thrombolysis and discuss the relationship between neuroinflammation and HT, which provides a reference for research on the mechanisms, prevention and treatment drugs, diagnosis and prognosis of HT.
出血性转化（HT）是缺血性卒中后常见且严重的并发症，尤其是在组织型纤溶酶原激活剂（t-PA）溶栓后，其与死亡率和残疾率增加相关。由于HT的机制和靶点尚不清楚，目前尚无有效的治疗药物来降低HT的发生率。近年来，许多研究发现神经炎症与t-PA溶栓后HT的发生发展密切相关，包括脑内胶质细胞活化、外周炎性细胞浸润以及炎性因子释放，涉及NF-κB、MAPK、HMGB1、TLR4和NLRP3等炎症相关靶点。一些具有抗炎活性的药物已在临床前实验和临床试验中显示出可保护血脑屏障并降低HT风险，包括米诺环素、芬戈莫德、他克莫司、他汀类药物以及一些天然产物。此外，MMP-9、VAP-1、NLR、sICAM-1等炎性因子的变化与HT的发生密切相关，可能是HT诊断和预后评估的潜在生物标志物。在本综述中，我们总结了t-PA溶栓后与HT相关的潜在炎症相关机制、靶点、治疗药物和生物标志物，并探讨了神经炎症与HT之间的关系，为HT的机制、预防和治疗药物、诊断和预后研究提供参考。
