Ghali George Zaki, Ghali Michael George Zaki
United States Environmental Protection Agency, Arlington, VA; Department of Toxicology, Purdue University, West Lafayette, IN, USA.
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
Neural Regen Res. 2020 Dec;15(12):2217-2234. doi: 10.4103/1673-5374.284981.
Nafamostat mesylate, an apparent soi-disant panacea of sorts, is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass, mitigate the inflammatory response in patients diagnosed with acute pancreatitis, and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East. The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia. Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases, neuroinflammatory signaling cascades, and the endoplasmic reticulum stress responses, downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents, modulating the activity of intracellular signal transduction pathways, and supporting neuronal survival (brain-derived neurotrophic factor/TrkB/ERK1/2/CREB, nuclear factor kappa B. The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture. Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac, hepatic, renal, or intestinal transplant, preventing allograft rejection, and treating solid organ malignancies. Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.
甲磺酸萘莫司他，一种貌似万灵药的药物，被广泛用于对接受血液透析或体外循环的患者进行抗凝，减轻被诊断为急性胰腺炎患者的炎症反应，以及逆转远东地区常见的濒死前弥散性血管内凝血患者的凝血病。丝氨酸蛋白酶抑制剂甲磺酸萘莫司他在神经血管缺血情况下表现出显著的神经保护作用。甲磺酸萘莫司他通过减弱丝氨酸蛋白酶的酶活性、神经炎症信号级联反应和内质网应激反应，下调兴奋性毒性瞬时受体膜通道亚家族7阳离子电流，调节细胞内信号转导途径的活性，并支持神经元存活（脑源性神经营养因子/TrkB/ERK1/2/CREB、核因子κB）来产生神经保护作用。这些作用共同减少神经元坏死和凋亡，并防止缺血介导的血脑屏障微结构破坏。这些化合物的临床研究应用可能减轻接受心脏、肝脏、肾脏或肠道移植患者的缺血再灌注损伤，预防同种异体移植排斥反应，并治疗实体器官恶性肿瘤。甲磺酸萘莫司他介导的神经保护作用支持在西方国家明智地开展随机前瞻性对照试验，以评估该化合物的临床效用。
