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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (5): 1000-1005. doi: 10.19723/j.issn.1671-167X.2022.05.029

• 论著 • 上一篇    下一篇

光生物调节加速脑组织间液引流及其机制

蔡颖1,2,万巧琴2,*(),蔡宪杰3,4,高亚娟1,5,韩鸿宾1,3,6,*()   

  1. 1. 北京大学第三医院放射科, 北京 100191
    2. 北京大学护理学院, 北京 100191
    3. 北京大学医学部医学技术研究院, 北京 100191
    4. 北京市磁共振成像设备与技术重点实验室, 北京 100191
    5. 国家药品监督管理局医学成像设备质量评价重点实验室, 北京 100191
    6. 北京大学深圳研究生院, 深圳 518055
  • 收稿日期:2022-03-22 出版日期:2022-10-18 发布日期:2022-10-14
  • 通讯作者: 万巧琴,韩鸿宾 E-mail:qqwan05@163.com;hanhongbin@bjmu.edu.cn
  • 作者简介:万巧琴, 北京大学医学部研究员, 北京大学长聘制副教授, 北京大学医学部智慧康养研究院副院长, 护理学院学科发展与科研管理办公室主任, 老年护理康复教研室副主任, 腾云照护研究中心副主任, 国家卫生健康委员会老年健康标准委员会委员, 中国研究型医院心脏康复学会青年常委, 北京老年学与老年健康学会常务理事。
    主要研究方向为老年护理与智慧康养、认知促进与运动康复; 围绕影响老年人生活质量的常见症状管理和干预, 以及老年照护体系建设方面开展系列研究。主持国家重点研发计划、国家自然科学基金等多项课题, 在国内外期刊发表论文100余篇, 其中SCI论文30余篇, 论文累计被引1 265次, 最高单篇被引215次, 其中1篇论文获Wiley Top Cited Article Award。已获发明专利1项, 软件著作权2项|韩鸿宾, 北京大学医学部教授, 博士生导师, 北京大学医学部医学技术研究院院长, 北京大学磁共振成像设备与技术实验室主任, 北京大学第三医院放射科主任医师, 国家药监局医学成像设备质量评价重点实验室主任, 中国医学装备协会磁共振成像装备与技术专业委员会主任委员, 中德转化医学协会荣誉会长, 国家产业基础专家委员会委员, 国际宇航科学院通讯院士。
    主要研究方向为医学成像新技术, 围绕脑细胞外间隙和类淋巴组织液开展脑病诊治相关研究。承担国家自然科学基金委重大仪器、国家杰出青年基金等科研项目30余项。在国内外核心期刊发表学术论文200余篇, 出版专著/译著5部, 获专利授权17项。入选教育部新世纪优秀人才计划、科技北京百名领军人才工程, 获华夏医学科技奖一等奖和中国青年科技奖, 成果入选2020年"中国十大医学科技新闻"
  • 基金资助:
    国家自然科学基金(61827808);国家自然科学基金(12126601);深圳市海外高层次人才"孔雀计划"(KQTD20180412181221912)

Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism

Ying CAI1,2,Qiao-qin WAN2,*(),Xian-jie CAI3,4,Ya-juan GAO1,5,Hong-bin HAN1,3,6,*()   

  1. 1. Department of Radiology, Peking University Third Hospital, Beijing 100191, China
    2. Peking University School of Nursing, Beijing 100191, China
    3. Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
    4. Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China
    5. NMPA Key Laboratory for Evaluation of Medical Imaging Equipment and Technique, Beijing 100191, China
    6. Peking University Shenzhen Graduate School, Shenzhen 518055, China
  • Received:2022-03-22 Online:2022-10-18 Published:2022-10-14
  • Contact: Qiao-qin WAN,Hong-bin HAN E-mail:qqwan05@163.com;hanhongbin@bjmu.edu.cn
  • Supported by:
    the National Nature Science Foundation(61827808);the National Nature Science Foundation(12126601);the Shenzhen Science and Technology Program(KQTD20180412181221912)

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摘要：

目的: 探讨光生物调节(photobiomodulation, PBM)对脑组织间液(interstitial fluid, ISF)引流的影响, 为PBM治疗阿尔兹海默病(Alzheimer’s disease)提供新的解释。方法: 24只SD雄性大鼠随机分为PBM组(n=12)、假PBM组(n=6)及空白对照组(n=6), 其中PBM组根据磁示踪分子探针注射部位的不同又分为PBM同侧示踪组(n=6)和PBM对侧示踪组(n=6)。PBM组和假PBM组大鼠在脑尾状核区ISF引流到达的额叶皮层区对应的颅骨上微创暴露硬膜; PBM组使用630 nm光纤(5~6 mW/cm2)按照每次光照5 min, 暂停2 min的方式, 总共照射5次; 假PBM组于相同位置使用光纤但不打开电源, 保持相同时间; 空白对照组不进行任何操作。PBM结束后, 将示踪分子探针注射到每组大鼠的尾状核区, 之后利用磁示踪技术根据探针分子的扩散和分布, 观察大鼠尾状核区ISF引流的变化规律, 并使用细胞外间隙(extracellular space, ECS)扩散参数图像(diffusion rate in ECS-mapping, DECS-mapping)技术分析脑ECS结构的变化, 最后得到反映脑ECS结构和ISF引流情况的参数: 容积占比(α)、迂曲度(λ)、半衰期(T1/2)和扩散参数(DECS)。比较各组间参数差异从而分析PBM对脑ECS及ISF的影响。结果: 参数T1/2、DECS和λ在PBM同侧示踪组、PBM对侧示踪组和假PBM组间差异有统计学意义(F=79.286, P＜0.001;F=13.458, P＜0.001;F=10.948, P=0.001), 而参数α在三组间差异无统计学意义(F=1.217, P=0.324)。与假PBM组和PBM对侧示踪组相比, PBM同侧示踪组的T1/2显著减小[(45.45±6.76) min vs. (76.01±3.44) min, P＜0.001;(45.45±6.76) min vs. (78.07±4.27) min, P＜0.001], 说明脑ISF引流速度明显加快; DECS显著增大[(4.51±0.77) ×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001;(4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P＜0.001], 说明脑ECS内分子扩散速率明显增快; λ显著减小(1.51±0.21 vs. 1.85±0.12, P=0.001;1.51±0.21 vs.1.89±0.11, P=0.001), 说明脑ECS结构的迂曲程度下降。结论: PBM可以调控脑ISF引流, 这可能是PBM治疗阿尔兹海默病的潜在作用机制之一, 也为经脑ECS途径提升脑功能的主动调控策略提供了全新方案。

关键词: 细胞外液, 光生物调节, 阿尔兹海默病, 放射性示踪剂, 磁共振成像

Abstract:

Objective: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). Methods: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. Results: The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. Conclusion: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

Key words: Extracellular fluid, Photobiomodulation, Alzheimer's disease, Radioactive tracers, Magnetic resonance imaging

中图分类号: 

  • R749.1

图1

示踪剂在不同分组大鼠尾状核区随时间变化的扩散分布"

表1

各组大鼠脑尾状核区ECS参数结果($\bar x \pm s$, n=6)"

Group T1/2/min DECS/(×10-4 mm2/s) α/% λ
Negative control 73.35±4.48 3.31±0.07 16.48±0.30 1.80±0.02
PBM-ipsilateral traced 45.45±6.76 4.51±0.77 16.61±0.48 1.51±0.21
PBM-contralateral traced 78.07±4.27* 3.01±0.38* 16.30±0.52 1.89±0.11*
Sham PBM 76.01±3.44* 3.15±0.44* 16.24±0.25 1.85±0.12*
Fa 79.286 13.458 1.217 10.948
Pa < 0.001 < 0.001 0.324 0.001

图2

不同分组大鼠尾状核区二维和三维细胞外间隙扩散参数图"

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ISSN 1671-167X
CN 11-4691/R
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