Glibenclamide is one kind of sulfonylureas,which was first used in clinical in 1969.Because of its pleiotropic protective effects in acute central nervous system (CNS) injury during the last decade,glibenclamide has drawn renewed attention from clinicians.Sulfonylurea receptor l(Sur1)-transient receptor potential melastatin 4(Trpm4) channel,called Surl,can regulate NCCa-ATP channel,which plays a key role in the inflammatory injury of cerebral hemorrhage,brain cell death and brain edema induced by cerebral ischemia.Studies showed that,acting via inhibition of the Sur1-Trpm4 channel and,in some cases,via brain KATP channels,glibenclamide could be beneficial in several clinically relevant rodent models of CNS diseases such as ischemic,hemorrhagic stroke,traumatic brain injury,spinal cord injury,neonatal encephalopathy of prematurity and metastatic brain tumor.Glibenclamide via inhibition of Surl shows activity in microvessels to reduce edema formation and secondary hemorrhage,inhibit necrotic cell death,exert potent anti-inflammatory effects and promote neurogenesis.At present,two clinical trials are undergoing,one of which is in patients with TBI and the other about stroke.Such studies in recent years have shown that Surl is involved in many acute pathological processes of CNS injury,and these studies provide a new opportunity for the use of glibenclamide,which is a safe drug but has not been used in the treatment of central nervous system diseases to date.%格列本脲是磺脲类药物的一种,1969年作为治疗Ⅱ型糖尿病的药物被首次引入临床.在近10年中由于其对急性中枢系统损伤的多效保护作用,格列本脲再次获得关注.磺脲类受体1 (Sur1)-瞬时受体电位通道M4型(Trpm4)通道在脑出血性炎症损伤、脑缺血导致的脑细胞死亡及脑水肿中发挥着关键作用.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,已经被证实在啮齿类动物模型的几种临床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、早产儿和新生儿脑病、转移性脑肿瘤.格列本脲通过抑制Sur1作用于微血管,减少脑水肿的形成和继发性出血,抑制坏死性细胞死亡、发挥强效抗炎作用和促进神经细胞再生.为了安全用药,格列本脲尚未被用于治疗人类中枢神经系统(CNS)相关疾病.目前正在进行的与之相关的两个临床实验是创伤性脑损伤和脑卒中.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.
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