格列本脲在脑出血水肿期的应用前景
Application Prospect of Glibenclamide in Cerebral Hemorrhage Edema
摘要: 格列本脲是磺脲类药物的一种，其作为口服降糖药的治疗益处可追溯到1971年。由于其对急性中枢系统损伤的多效保护作用，在近十年中格列本脲再次被关注。格列本脲通过抑制磺脲类受体1 (Sur1)发挥作用。Sur1-瞬时受体电位通道M4型(Trpm4)通道通过使细胞去极化，并允许钠向内流动和钾流出，从而促进水肿的形成，在缺血性和出血性CNS损伤中及脑水肿中发挥着关键作用。脑出血后脑水肿是脑实质内水分的积聚，包括细胞毒性水肿、血管源性水肿和流体静力性水肿。格列本脲通过抑制Sur1-Trpm4通道以及在某些情况下抑制大脑的ATP敏感性钾通道，已经被证实在动物模型的相关疾病中有治疗作用，如：缺血性和出血性脑卒中、外伤性脑损伤、脊髓损伤、转移性脑肿瘤。目前正在进行的相关临床实验有出血性脑卒中和缺血性脑卒中及创伤性脑损伤。这些实验表明Sur1参与了多种中枢神经系统损伤的有关急性病理过程，为临床使用格列本脲提供了新的支持依据。本综述的目的是突出格列本脲在治疗脑损伤中的潜在作用，并提出临床证据支持格列本脲在脑出血中的治疗潜力。
Abstract: Glibenclamide is a class of sulfonylureas whose therapeutic benefits as oral hypoglycemic agents date back to 1971. Glibenclamide has attracted renewed attention in recent ten years due to its multipotent protective effect against acute central system injury. Glibenclamide works by inhibiting sulfonylurea receptor 1 (Sur1). Sur1-transient receptor potential channel TYPE M4 (Trpm4) channels play a key role in ischemic and hemorrhagic CNS injury and cerebral edema by depolarizing cells and allowing sodium inward flow and potassium outflow. Cerebral edema after intracerebral hemorrhage is the accumulation of water in the brain parenchyma, including cytotoxic edema, vasogenic edema and hydrostatic edema. Glibenclamide has been shown to be therapeutic in animal models of related diseases, such as ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, and metastatic brain tumors, by inhibiting sur1-TRPM4 channels and, in some cases, ATP-sensitive potassium channels in the brain. Ongoing clinical trials include hemorrhagic stroke, ischemic stroke and traumatic brain injury. These experiments indicated that Sur1 was involved in various acute pathological processes related to central nervous system injury, providing new support for clinical use of glibenclamide. The purpose of this review is to highlight the potential role of glibenclamide in the treatment of brain injury and to present clinical evidence supporting the potential of glibenclamide in the treatment of cerebral hemorrhage.
文章引用：李娟, 王涛, 师宁, 冯鑫慧. 格列本脲在脑出血水肿期的应用前景[J]. 临床医学进展, 2021, 11(11): 5492-5500. https://doi.org/10.12677/ACM.2021.1111813

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