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背景:近年来有新的基础医学和临床研究结果提示,脊髓损伤后早期即出现骨吸收增加和骨量下降,其病理阶段起始早于单纯失用性骨质疏松,表明有其他机制参与脊髓损伤导致的骨质疏松症的发病过程。目的:通过文献检索,分析中枢神经系统内主要神经递质包括多巴胺和5-羟色胺及其受体系统对骨代谢的影响、在脊髓损伤后的病理变化以及相关受体作为靶点对脊髓损伤的治疗性研究,综述相关基础和临床科研现状及进展,提出关于脊髓损伤导致的骨质疏松症发病机制的新理论和诊疗策略。方法:检索1967年1月至2016年8月Pub Med数据库和Embase数据库中有关脊髓损伤后继发性骨质疏松症与神经递质多巴胺和5-羟色胺及其受体系统相关的基础和临床研究文献。英文检索词包括“spinal cord injury;osteoporosis;dopamine;serotonin;5-hydroxytryptamine”。排除与研究目的无关、相关性差或内容重复的研究。结果与结论:多巴胺和5-羟色胺是中枢和外周神经系统主要神经递质,对骨吸收和重建均起调节作用。脊髓损伤发生后中枢神经系统内下行的多巴胺和5-羟色胺作用途径受损,随后多巴胺受体系统和5-羟色胺受体系统的作用变化将导致骨吸收增加和骨重建受损。通过了解脊髓内多巴胺受体系统和5-羟色胺受体系统在脊髓损伤导致的骨质疏松症发病过程中的作用,推测可将多巴胺和5-羟色胺受体作为治疗靶点。现有研究指出部分多巴胺和5-羟色胺受体激动剂可改善脊髓损伤后运动功能,提示相关制剂作用于损伤平面以下多巴胺和5-羟色胺受体同时可能抑制骨吸收并促进骨重建,为脊髓损伤导致的骨质疏松症、其他类型继发性骨质疏松症和原发性骨质疏松症提供全新的预防或治疗途径。
BACKGROUND: In recent years, new basic medical and clinical studies have shown that there is an increase in bone resorption and bone mass loss early after spinal cord injury. The pathological stage starts earlier than simple disuse osteoporosis, indicating that there are other mechanisms involved in the spinal cord Damage caused by the pathogenesis of osteoporosis. OBJECTIVE: To analyze the effects of major neurotransmitters including dopamine and serotonin and its receptor system on the bone metabolism in the central nervous system through literature search. The pathological changes after spinal cord injury and the related receptors as targets of spinal cord injury Therapeutic research, review the relevant basic and clinical research status and progress, put forward a new theory and diagnosis and treatment strategy on the pathogenesis of osteoporosis caused by spinal cord injury. METHODS: We searched the Pub Med and Embase databases from January 1967 to August 2016 for basic and clinical literature related to the occurrence of secondary osteoporosis after spinal cord injury in relation to the neurotransmitters dopamine and serotonin and their receptor systems . English terms include “spinal cord injury; osteoporosis; dopamine; serotonin; 5-hydroxytryptamine”. Excludes studies that have nothing to do with the purpose of the study, are of poor relevance, or have duplicates. RESULTS AND CONCLUSION: Dopamine and serotonin are the main neurotransmitters in the central and peripheral nervous system and play a regulatory role in bone resorption and remodeling. Dopamine and serotonin pathways are impaired within the central nervous system following spinal cord injury, and subsequent changes in the dopamine receptor system and the serotonin receptor system lead to increased bone resorption and impaired bone remodeling. By understanding the role of the spinal cord dopamine receptor system and the serotonin receptor system in the pathogenesis of osteoporosis induced by spinal cord injury, it is speculated that dopamine and serotonin receptors can be used as therapeutic targets. Existing studies indicate that some dopamine and serotonin receptor agonists can improve motor function after spinal cord injury, suggesting that the relevant agents acting on the lesion below the level of dopamine and serotonin receptors may inhibit bone resorption and promote bone remodeling, spinal cord injury Leading to osteoporosis, other types of secondary osteoporosis and primary osteoporosis provide a new way to prevent or treat.