摘要
高原特殊环境下,机体皮肤会出现一系列适应性反应和病理性变化,这些变化包括皮肤屏障功能受损、皮肤血管收缩障碍、角质层异常增厚、纤维素沉积等,导致高原地区皮肤疾病的发病率相对较高。研究表明,高原环境中皮肤微生物的组成和多样性会发生变化,这可能与皮肤疾病的发生、发展密切相关。本文旨在综述高原环境对皮肤的影响、高原常见皮肤病,以及微生物对皮肤疾病的影响,并探讨高原环境下皮肤微生物群对皮肤疾病的影响及作用机制。
高原地形在全球分布极为广泛,约占陆地总面积的45%。我国也是一个高原地形广布的国家,其中青藏高原是我国第一大高
皮肤作为机体与环境之间最大的界面,能直接且敏锐地感知环境的变化,从而有效抵御来自外部环境的伤
1 高原环境对皮肤的影响
地理学上,将海拔在500 m以上、顶面平缓、面积辽阔且边界清晰的高地称为高原。医学上所说的高原是指海拔在2 500 m以上,能产生明显生理学效应的地
皮肤作为覆盖人体的最大器官,能够敏锐地感知到氧含量的波动。在低氧条件下,缺氧诱导因子1α (hypoxia-inducible factor 1α, HIF-1α)被激活,进而调节皮肤成纤维细胞及角质形成细胞的黏附和迁移,引起皮肤血管收缩,导致血流量减少,表明HIF-1α的表达与皮肤内稳态变化密切相
2 高原环境导致的皮肤疾病
在高原特殊环境下,机体皮肤会出现一系列适应性反应和病理性变化,这些变化包括皮肤屏障功能受损、皮肤血管收缩障碍、角质层异常增厚、纤维素沉积等,导致高原地区皮肤疾病的发病率相对较高,尤其是日光性皮炎、光老化和冻疮等皮肤疾病易发、多
2.1 日光相关性皮肤疾病
日光作为重要的环境因素,对机体健康具有双重影响。适度的日光照射对机体有益,如改善血液循环、促进维生素D合成及微量元素吸
高原地区大气层较薄,多属日光照射丰富区,大量日光辐射会增加紫外线暴露。对于急进高原人群而言,强紫外线照射极易导致晒伤、神经性皮炎的发生。晒伤的症状与体征通常在紫外线照射后1-24 h内出现,皮肤的改变从轻度的红斑发展到表浅的鳞屑及水疱的产生,还会引起皮肤疼痛,严重者会出现感染、永久性斑点色素沉着等症
久居高原人群因长期处于强紫外线环境中,更容易出现日光性皮炎、光老化、日光性角化病和皮肤癌等疾病。日光性皮炎是高原常见皮肤病,通常在春末夏初高发,临床表现为局部皮肤充血,继而出现红肿,甚至破溃,且有触压过敏现象,严重者还可引起全身不良反
2.2 寒冷损伤性皮肤疾病
高原地区海拔高,气温低,寒冷时间长,形成了独特的高寒气候。Dow
越来越多的研究表明,在高海拔地区,低氧会加重冻伤的程度。Yang
2.3 干燥相关性皮肤疾病
高原环境的低温、干燥、强风、温差大等因素均可造成皮肤表皮屏障水分丢失、皮脂减少,诱导皮肤出现干燥、瘙痒、皲裂和渗出等症状。通过对急进高原某部队深入调查,发现官兵皮肤的干燥、皲裂状况占到62%,而冻疮则仅为15
3 皮肤微生物群概述
3.1 皮肤微生物群的组成
人体微生态系统主要由皮肤、口腔、泌尿及胃肠道构成,各系统间相互协同,其中肠道微生态系统最为复杂且丰富,已被广泛研究,而皮肤微生态系统近年来才逐渐受到关
根据微生物的形态特征,皮肤微生物群通常分为细胞型微生物和非细胞型微生物(

图1 皮肤微生物的组成
Figure 1 Composition of skin microorganisms.
根据与宿主的共生关系,皮肤微生物群还可分为共生菌和致病
3.2 皮肤微生物群的影响因素
皮肤微生物群是一个庞杂而动态的群落,其稳态是评价皮肤健康状况的重要指标。目前已知多种因素可影响皮肤微生物群落的动态平衡,主要包括内源性因素(皮肤结构和皮肤区域)和外源性因素(环境暴露);这些复杂的影响因素共同决定了皮肤微生物群在维持皮肤环境内稳态和影响皮肤疾病发生发展的作
在一定程度上,皮肤结构决定了微生物群落的组成。皮肤作为人体的天然屏障,由表皮和真皮组成,大量微生物寄居于表皮层。共生菌群在表皮层中占绝对优势,主要包括放线菌门、厚壁菌门、葡萄球菌属和棒状杆菌属等,在维持皮肤屏障中具有关键作
除皮肤的分层结构外,皮肤区域也是调控个体皮肤微生物异质性的关键因素。腹股沟和腋窝等较湿润的部位为葡萄球菌、棒状杆菌和β-变形杆菌的繁殖提供了理想的生存环境;颜面和胸背等富含皮脂腺的部位会促进亲脂性微生物,如丙酸杆菌和马拉色菌的生长;而四肢等干燥的部位其微生物群落具有丰富的多样
尽管皮肤结构和皮肤区域等内在因素对皮肤微生物的塑造具有重要的影响,但环境暴露对皮肤微生物群物种组成及功能特征的影响更为显著。王逸
4 皮肤微生物群与高原常见皮肤疾病的关系
4.1 高原环境对皮肤微生物群的影响
环境因素与皮肤微生物群的改变紧密相关,然而,当前研究主要聚焦于高原特有物种,而对于高原居民皮肤微生物群落的物种组成及功能特性的探究则相对较少。小头裸裂尻鱼是青藏高原特有的鱼类,利用高通量测序发现其皮肤黏膜微生物中放线菌门和变形菌门为优势菌门,推测可能与小头裸裂尻鱼适应高原低温、低氧环境有
4.2 皮肤微生物稳态改变与皮肤相关疾病
皮肤微生物稳态对于维持皮肤健康至关重要。大量研究表明,皮肤微生物群参与多种皮肤疾病的发生发展过程。Edslev
皮肤微生态的失衡与特应性皮炎、痤疮、银屑病及皮肤炎症的发生发展有密切相关,因此,可以尝试以修复皮肤微生物动态平衡为切入点,调节皮肤微生物群,恢复皮肤屏障,减少炎症反应,以期在皮肤病的治疗中获得良好的效果。近年来,随着对微生态制剂研究的不断深入,以益生菌、益生元和合生元为代表的微生态制剂,不仅具有抵抗、抑制病原菌生长繁殖的特性,还能增强固有免疫系统和免疫耐受机
4.3 高原条件下皮肤微生态的变化与皮肤疾病
由于急进高原和久居高原者受到高原特殊环境的影响,皮肤微生物群结构及多样性发生改变,导致皮肤屏障功能及抵御病原体的能力发生变化,从而影响皮肤的稳定性并增加感染的可能性,使得罹患皮肤疾病的几率增大,且容易反复发

图2 高原环境下皮肤微生物变化引起皮肤疾病的发生机制
Figure 2 Mechanisms of dermatologic disorders caused by microbial changes in the skin in plateau environments.
在高原环境下皮肤微生物多样性相对较低,一些低氧、紫外线敏感的微生物及其代谢产物的相对丰度发生变化,从而诱导抗菌肽及细胞因子的表达,使皮肤抵御病原体入侵的能力减弱,加重皮肤炎症反应,进而导致特应性皮炎、异位性皮炎等慢性复发性皮肤炎症疾病的发
综上所述,对皮肤菌群特征的全面理解是对高原皮肤疾病认识的前提,也是应用微生物制剂对高原皮肤病进行靶向干预、预防和治疗的基础。因此,未来应利用功能性的多组学方法(如16S rRNA基因、宏基因组、宏转录组和宏蛋白组等)从微生物多样性、种群结构、进化关系、功能活性等方面来表征高原特殊环境下皮肤微生物群变化与常见皮肤疾病的关系,筛选出与高原皮肤病相关的特定微生物种/株/代谢产物,从而开发和优化各种体外微生物组培养模型,将微生物组整合到未来的预防和治疗策略中,为高原皮肤病的诊断与治疗带来新的希
5 总结与展望
皮肤作为人体与外界环境最大的交互界面,寄居着数量庞大的微生物群。这些微生物之间相互制约、共存,最终形成了微妙的生态平衡。大量研究表明,皮肤微生物与皮肤疾病的发生密切相关。例如,葡萄球菌属的相对丰度增加可能引发特应性皮炎,而痤疮丙酸杆菌的大量繁殖则可能导致痤
高原地区普遍具有低气压、低氧含量、寒冷干燥等独特的环境特征,这些环境因素会对人体产生不同程度的影
由于皮肤微生物群组成的复杂性和分析技术的局限性,使得皮肤微生物群的研究仍面临巨大挑战。此外,高原不仅具有低压、低氧、强辐射等环境特征,且长期“偏远化、多元化、滞后化”的社会现状,进一步加剧了高原常见皮肤疾病研究的难
随着测序技术和分析方法的不断进步,我们对皮肤微生物群落有了更深入的认识。目前,关于高原特殊环境下皮肤微生物的改变在维持机体皮肤稳态或加剧皮肤疾病中所扮演的角色仍不清楚。我们可以通过全基因组、宏基因组测序来表征微生物序列数据,整合现有数据库资源,构建高原地区人群皮肤微生物基因目录,并筛选出具有潜在生物标记物功能的致病菌、特征菌及微生物代谢物。进一步地,可以利用单体分离或培养等方法来获得这些可能的致病菌、特征菌及微生物代谢物,并分析其功能。在动物模型中进行验证,从而揭示高原特殊环境中皮肤菌群生态变化与皮肤疾病的关联,并探索消除相应病原体的有效方
作者贡献声明
白雪:全文撰写、绘图并核对论文内容;杨建鑫:对论文进行整体的指导和修改。
利益冲突
作者声明不存在任何可能会影响本文所报告工作的已知经济利益或个人关系。
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