低强度电磁场对骨的非热生物学“频率窗”效应及其机理的研究

Wide existence of non-thermal biological frequency-window effects on bone induced by low-intensity electromagnetic fields (LEMFs) is the major cause for those differences in various experimental results and its mechanisms. Therefore, we propose the hypothesis that the quantal resonance induced by LEMFs with specific spectrum might be the cause for the occurrence and development of biological effects on bone. To test the hypothesis, the experiment scheme is designed from three aspects: (1) We will establish a mathematical model of quantal resonance, comprehensively analyse the energy transformation of nucleon in bone under the exposure in both geomagnetic fields and LEMFs, and seek a method for screening frequency-window parameter; (2) We will investigate the sensitivity of quantal resonance to the inherent electromagnetic parameters such as dipole moments, rotation constant and resonant spectra of molecules. Furthermore, the protein sequences which are sensitive to quantal resonance in the kinase family would be searched. In addition, we will investigate the effects of quantal resonance to 3D spatial conformation of protein sequences; (3) We will develop a new type of LEMFs stimulator that can output LEMFs with specific window-frequency. With this LEMFs apparatus, we will investigate the non-thermal biological frequency-window effects induced by quantal resonance on bone by conducting series of medical experiments. In summary, the experimental design goes from system, tissue, cell, to molecule. Moreover, the experimental scheme employed in our study combined with engineering and medicine, macroscopic and microscopic perspectives, both in vitro and in vivo. The experimental repeatability for this research might also be enhanced. The study provides a new idea and theoretic basis not only for revealing the mechanism of non-thermal biological effects of LEMFs on bone but also for the wide application of magnetic therapy.

低强度电磁场对骨的非热生物学“频率窗”效应是导致该领域研究结果各异、机制不明的主要原因。基于此，本课题首次提出“特定频谱LEMFs激发的骨内生物核子量子共振是诱发骨生物效应”的假说，并从三个层面进行验证：(1)建立量子共振数学模型，分析骨内生物核子在地磁和LEMFs双重辐照下的能量转化过程，提出LEMFs“窗频率”参数筛选的理论方法；（2）探究骨内生物分子的偶极矩、转动常数、振动谱等固有电磁特性对共振的敏感性，探寻共振敏感的蛋白激酶序列片段，并研究共振对其三维空间构象的影响；(3)研发新型磁场发生装置，结合体内体外实验，验证量子共振诱发的“频率窗”效应。实验方案由“系统→组织→细胞→分子”层层深入，工学与医学、宏观与微观、在体与离体相结合，为筛选“窗频率”参数提供科学合理的解决方案，提高该领域研究的可重复性，有望为系统揭示电磁场对骨的非热生物效应作用机理和磁疗的应用提供新的思路与理论依据。

低强度电磁场（low-intensity electromagnetic fields，LEMF）作为一种重要的物理因子，已成为生物物理领域的研究热点，并在治疗骨相关疾病具有很好的推广价值和潜力。但是，LEMFs对骨的非热生物效应的研究结果与结论五花八门，有关其发生机制的阐述众说纷纭。此外，由于各研究小组搭建使用的研究平台不尽相同，实验研究的可重复性不高，导致人们对其科学性存有质疑，使磁疗在骨的临床上的应用与推广受阻。有报道表明，LEMF对OBs的主要影响与时域中LEMF的参数无关，应鼓励分析扩展到LEMF的频域特性。.因此，重点研究LEMF频谱可能有助于探明LEMF对OP效应的可能机制。有很好的证据表明，当LEMF的频率与关键离子的回旋频率相匹配时，会产生共振效应，该效应影响离子通过膜通道的速率进而产生其他系列生物效应。因而，本项目主要研究了以下内容：（1）研制能产生不同频段LEMF的发生装置；（2）不同频段LEMF对小鼠MC3T3-E1成骨前体细胞增殖和分化成熟的影响；（3）不同频段LEMF对RANKL诱导小鼠RAW 264.7破骨前体细胞增殖和分化成熟的影响；（4）不同频段LEMF对OVX小鼠OP的影响。（5）LEMF对骨的“频率窗”效应基本物理机制的数值分析。.研究结果发现：(1)ICR频段相关的LEMF显著促进骨形成活性，并间接促进骨吸收活性。然而，OVX诱导的OP小鼠中骨吸收仍占主导地位，因而LP，BP对OVX诱导的OP小鼠中降低的骨量和退化的骨微结构和机械强度的效果有限。（2）高频段不仅急剧降低骨形成活性，而且显著降低骨吸收活性。因而，HP对OVX诱导的OP小鼠中降低的骨量和退化的骨微结构和机械强度的效果也不佳。（3）均包含ICR频段与高频段的AP既可显著促进骨形成活性又可显著降低骨吸收活性，最终可降低OVX诱导的OP小鼠的骨丢失。（4）ICR频段相关的LEMF对OBs有积极影响，高频LEMF对OBs和OCs有副作用。合理结合不同频段对成骨和破骨的作用，是治疗OP的关键。.本项目系统验证了不同频段LEMF对成骨和破骨的效应，为揭示LEMF对骨的非热生物效应作用机理提供了新的思路与实验依据。