Liu Jia-Cheng, Lei Shuang-Yin, Zhang Dian-Hui, He Qian-Yan, Sun Ying-Ying, Zhu Hong-Jing, Qu Yang, Zhou Sheng-Yu, Yang Yi, Li Chao, Guo Zhen-Ni
Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1#, Changchun, 130021, China.
Jilin Provincial Key Laboratory of Cerebrovascular Disease, Xinmin Street 1#, Changchun, 130021, China.
Mol Med. 2024 Dec 20;30(1):256. doi: 10.1186/s10020-024-01025-0.
The blood-brain barrier (BBB) is the most central component of the neurovascular unit (NVU) and is crucial for the maintenance of the internal environment of the central nervous system and the regulation of homeostasis. A multitude of neuroprotective agents have been developed to exert neuroprotective effects and improve the prognosis of patients with ischemic stroke. These agents have been designed to maintain integrity and promote BBB repair. Statins are widely used as pharmacological agents for the treatment and prevention of ischemic stroke, making them a cornerstone in the pharmacological armamentarium for this condition. The primary mechanism of action is the reduction of serum cholesterol through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which results in a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in cholesterol clearance. Nevertheless, basic and clinical research has indicated that statins may exert additional pleiotropic effects beyond LDL-C reduction. Previous studies on ischemic stroke have demonstrated that statins can enhance neurological function, reduce inflammation, and promote angiogenic and synaptic processes following ischemic stroke. The BBB has been increasingly recognized for its role in the development and progression of ischemic stroke. Statins have also been found to play a potential BBB protective role by affecting members of the NVU. This review aimed to provide a comprehensive theoretical basis for the clinical application of statins by systematically detailing how statins influence the BBB, particularly focusing on the regulation of the function of each member of the NVU.
血脑屏障（BBB）是神经血管单元（NVU）的核心组成部分，对于维持中枢神经系统的内环境和体内平衡的调节至关重要。已经开发了多种神经保护剂来发挥神经保护作用并改善缺血性中风患者的预后。这些药物旨在维持完整性并促进血脑屏障修复。他汀类药物被广泛用作治疗和预防缺血性中风的药物，使其成为治疗这种疾病的药物库中的基石。其主要作用机制是通过抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶来降低血清胆固醇，从而导致低密度脂蛋白胆固醇（LDL-C）降低和胆固醇清除增加。然而，基础和临床研究表明，他汀类药物可能在降低LDL-C之外还发挥其他多效性作用。先前关于缺血性中风的研究表明，他汀类药物可以增强神经功能、减轻炎症，并促进缺血性中风后的血管生成和突触形成过程。血脑屏障在缺血性中风的发生和发展中的作用越来越受到认可。还发现他汀类药物通过影响神经血管单元的成员发挥潜在的血脑屏障保护作用。本综述旨在通过系统详细地阐述他汀类药物如何影响血脑屏障，特别是关注神经血管单元各成员功能的调节，为他汀类药物的临床应用提供全面的理论基础。
