摘要
酒精使用障碍是世界上严重的公共卫生与健康问题。慢性酒精暴露能引起慢性酒精中毒性脑病等各类神经、精神疾病。神经炎症是造成各类神经系统疾病的关键病理学基础。过去在药物研发方面,通过调控磷酸二酯酶(phosphodiesterase, PDE),改善免疫反应失调已非常广泛,也普遍应用于临床上治疗各类神经炎症。虽然过去有文献证实,慢性酒精暴露会通过调控PDE引发免疫反应失调,诱发炎症相关疾病。然而调控磷酸二酯酶的药物仅有少部分处于临床试验阶段,还未用于治疗由慢性酒精暴露所致的神经炎症。在慢性酒精暴露所致神经炎症中目前还未找到完整的致病信号通路,对于PDE所受的调控机制了解也十分有限,其中包括表观遗传等机制。而大量对于慢性酒精暴露所致神经炎症的研究中,发现神经系统内PDE和miRNA表达量失调与炎症反应高度关联,但还未确证两者之间具体的相互作用关系。不过在非神经炎症的疾病中,已找到大量miRNA-PDE这类调控炎症、细胞凋亡等致病因子的机制。本文将对慢性酒精暴露后所引发的神经炎症以及miRNA-PDE对其调控的机制进行综述,为实现精准靶向治疗慢性酒精暴露引起的神经系统病变提供新思路。
Alcohol use disorder(AUD)is a serious public health and health problem in the world.Chronic alcohol exposure can cause various neurological and psychiatric diseases such as chronic alcoholic encephalopathy.Neuroinflammation is the key pathological basis for various neurological diseases.In the past,drug development has been very widely used to improve immune dysregulation by regulating phosphodiesterase(PDE),and it should also be used in the clinical treatment of various neuroinflammation.Although it has been confirmed in the past that chronic alcohol exposure will cause immune dysregulation by regulating PDE and produce inflammation-related diseases.However,at present,such drugs have not been used to treat neuroinflammation caused by chronic alcohol exposure,and only a small number of them are in the clinical trial stage.Accordingly,a complete pathogenic signaling pathway hasn't been found in the neuroinflammation caused by chronic alcohol exposure,and the understanding of the regulatory mechanism of PDE is also very limited,including epigenetic mechanisms.In many studies on the neuroinflammation caused by chronic alcohol exposure,it has been found that the expression of PDE and miRNA in the nervous system is highly correlated with inflammatory reactions,but the specific interaction between the two has not been confirmed.However,in nonneuroinflammatory diseases,many miRNA-PDE mechanisms have been found to regulate inflammation,apoptosis,and other pathogenic factors.In this paper,the neuroinflammation induced by chronic alcohol exposure and the mechanism of miRNA-PDE regulation are reviewed,which provides new ideas for the accurate targeted treatment of nervous systemdiseases caused by chronic alcohol exposure.
作者
吴劭皇
于浩
张国华
王晓龙
WU Shao-huang;YU Hao;ZHANG Guo-hua;WANG Xiao-long(Department of Forensic Pathology,China Medical University School of Forensic Medicine,Shenyang 110122,China;Liaoning Province Key Laboratory of Forensic Bio-evidence Sciences,Shenyang 110122,China;China Medical University Center of Forensic Investigation,Shenyang 110122,China)
出处
《中国药物依赖性杂志》
CAS
CSCD
2024年第4期273-279,共7页
Chinese Journal of Drug Dependence
基金
中国医科大学大学生创新训练计划项目(202310159019,X202210159009)
国家自然科学基金(82101979,82271931,81172904)
辽宁省自然科学基金(2022-MS-220)
辽宁省博士科研启动基金(2019-BS-145)。
