摘要
背景:低温对人的心血管系统存在不利影响,尤其是生活在寒冷气候的人群中,高血压和相关心血管疾病的患病率更高。瞬时受体电位M8常被认为是环境寒冷的生理传感器,而谷氨酸受体3/海人藻酸型亚基2(GLR-3/GluK2)亦具有冷敏感性。然而寒冷相关的瞬时受体电位M8及GLR-3/GluK2在调节高血压中的具体分子机制仍令人困惑。目的:拟通过对该领域文献的回顾,寻找瞬时受体电位M8及GLR-3/GluK2调控机体冷反应的一般规律,以及在高血压中的特殊作用机制,为后续基于冷刺激相关靶点治疗高血压的研究提供理论依据,进一步拓展高血压治疗的新思路和新方法。方法:采用文献资料法,通过对有关“寒冷刺激、瞬时受体电位M8、GLR-3/GluK2以及高血压”等相关文献的检索、查阅和筛选,为全文的分析奠定理论基础。采用对比分析法,通过对所得到文献进行阅读分析比较文献之间的异同点,为论点提供合理的理论支撑。通过对文献的进一步对比分析,厘清相关指标间的关系,为全文的分析明确思路。结果与结论:①瞬时受体电位M8能够被寒冷激活,并在哺乳动物中主要介导凉爽温度感知;它的激活可触发神经源性炎症反应,间接影响炎症进程;瞬时受体电位M8信号异常会导致免疫细胞过度活化,与高血压的发生和发展存在显著关联;②GLR-3/GluK2的激活阈值低于瞬时受体电位M8,可能优先响应有害寒冷刺激而非普通凉爽温度;寒冷环境下,GLR-3/GluK2激活后通过调控神经元间信号传导增强交感神经兴奋性,引发外周血管收缩;长期作用可导致外周血管阻力升高;③提示瞬时受体电位M8和GLR-3/GluK2分别通过感知不同强度的寒冷刺激,参与神经-免疫-血管系统的交互调控;瞬时受体电位M8信号异常通过炎症和免疫失调间接促进高血压进程,而GLR-3/GluK2则通过增强交感神经活性直接加剧血管收缩及阻力升高;两者共同作用可能构成寒冷环境下高血压发生发展的关键分子机制,为干预寒冷相关心血管疾病提供了潜在靶点。
BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body’s cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on“cold stimulation,TRPM8,GLR-3/GluK2 and hypertension”to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.
作者
王京峰
夏帆
毛苏杰
李晓琳
Wang Jingfeng;Xia Fan;Mao Sujie;Li Xiaolin(Harbin Sports University,Harbin 150008,Heilongjiang Province,China)
出处
《中国组织工程研究》
北大核心
2026年第6期1499-1507,共9页
Chinese Journal of Tissue Engineering Research
基金
哈尔滨体育学院实验室平台专项(LAB2021-06),项目负责人:李晓琳
黑龙江省自然科学基金(LH2022C051),项目参与人:李晓琳。
作者简介
第一作者:王京峰,男,1997年生,山东省泰安市人,汉族,在读博士,主要从事运动人体科学研究,https://orcid.org/0000-0002-9581-6381;通讯作者:李晓琳,博士,博士生导师,教授,哈尔滨体育学院研究生院,黑龙江省哈尔滨市150008。
