多巴胺和5-羟色胺受体系统参与脊髓损伤后继发性骨质疏松症发病:新理论和诊疗策略（英文）  

Dopamine and 5-hydroxytryptamine signaling pathways in the pathogenesis of spinal cord injury-induced osteoporosis: new theory and novel therapeutic strategies

作　　者：张淼[1] 张旭然[1] 李锐[2] 孙羽[3] 

机构地区：[1]阜新市中心医院骨科三病房,辽宁省阜新市123000 [2]吉林大学第二医院骨科诊疗中心,吉林省长春市130041 [3]中国医科大学附属第一医院骨外科(关节外科和运动医学病房),辽宁省沈阳市110001

出　　处：《中国组织工程研究》2016年第51期7731-7737,共7页Chinese Journal of Tissue Engineering Research

基　　金：the National Key Basic Research Development Program of China(973 Program),No.2014LB542200~~

摘　　要：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：Current basic and clinical research have showed that increases in bone resorption and bone loss accur earlier after spinal cord injury （SCI） than disuse atrophy, revealing that other mechanisms are involved in the pathogenesis of the SCI-induced osteoporosis （SIO）. OBJECTIVE：To introduce the current lab and clinical research progress in SIO focusing on the functional changes of two major neurotransmitters in the spinal cord, including dopamine （DA）, 5-hydroxytryptamine （5-HT） and their receptors, as well as their regulatory functions on bone metabolism, aiming at finding a new treatment strategy for SIO. METHODS：A computer-based online search in PubMed and Embase databases was conducted for clinical and basic research related to SIO published from January 1967 to August 2016, using the keywords of“spinal cord injury;osteoporosis;dopamine;serotonin;5-hydroxytryptamine”in English. Irrelevant, poorly related and repetitive studies were excluded, and finally 41 eligible articles were included. RESULTS AND CONCLUSION：DA and 5-HT are major neurotransmitters in the central nervous system, both involving in the regulation of bone remodeling. After SCI, loss of innervation and descending neurotransmitters especially DA, 5-HT and subsequent deregulation of their receptors are responsible for the onset of post-traumatic bone loss. The above research progress, in combination with the emerging clinical and lab investigations targeting 5-HT, DA and their receptors for improving neural functions after SCI, provides possible therapeutic pathways for SIO.

关 键 词：脊髓损伤 骨质疏松 多巴胺 血清素 组织工程 组织构建 骨组织工程 骨吸收 骨重建 5-羟色胺 神经递质 受体激动剂 

分 类 号：R318[医药卫生—生物医学工程]