论文总字数：28336字

摘 要

近年来发现催产素能直接调节骨代谢的生理功能，结合磁场对神经内分泌的调节作用，磁场和磁性纳米颗粒对骨生长的促进作用，本课题研究利用绝经后骨质疏松小鼠模型，通过下丘脑室旁核立体定位注射磁性纳米颗粒并在外加旋转磁场作用下探讨催产素对骨代谢的调节，综合运用骨生物学、生物化学等领域的多种实验方法和检测技术，探讨催产素对骨代谢的调节。实验研究中通过切除双侧卵巢制备小鼠骨质疏松模型，利用脑定位仪立体定点于小鼠室旁核处注射磁性纳米颗粒，并外加旋转磁场作用一个月后，再通过MICRO-CT设备测得小鼠骨密度并获取骨骼横截面结构图，以及通过摘除小鼠眼球取血测定血清中成骨标志物BALP和破骨标志物TRACP的含量。实验结果：切除卵巢6周后的小鼠的骨密度明显低于对照小鼠（Plt;0.05），血清中BALP和TRACP的含量显著降低（Plt;0.05），验证了骨质疏松小鼠造模成功。对比对照组（c组）,骨质疏松造模组（o组），室旁核磁性纳米颗粒注射组（on组）和室旁核磁性纳米颗粒注射外加磁场作用组（onm组）的左侧股骨骨结构差异、CT值差异以及血清内BALP和TRACP含量的差异，o组左侧股骨表现出明显骨丢失，CT值较c组显著性降低（Plt;0.001），血清内BALP和TRACP含量较c组显著减少（Plt;0.05）并且主要表现为骨生成显著减少（Plt;0.001）；on组左侧股骨表现出较弱骨丢失，CT值显著性降低（Plt;0.001），血清内BALP含量较o组显著增加（Plt;0.001），TRACP含量和o组无明显差异且显著低于c组（Plt;0.05）；onm组左侧股骨表现出骨生成增加，CT值显著高过o组和on组（Plt;0.01），血清内BALP含量较o组和on组极显著增加（Plt;0.001），TRACP含量较o组和on组显著增加（Plt;0.05），并且主要表现为骨生成显著增加（Plt;0.001）。证实了小鼠脑室旁核处注射磁性纳米颗粒并于磁场作用下可能增加骨代谢活动，发挥促进骨生成，骨重建的作用。实验研究结果表明了室旁核磁刺激对骨代谢的调节作用，并暗示了催产素在骨质疏松病上可能拥有积极的治疗作用。

关键词：骨质疏松，催产素，骨代谢，磁性纳米颗粒，磁场

ABSTRACT

In recent years, it has been found that oxytocin can directly regulate bone metabolism, this study combined with the regulation of neuroendocrine by magnetic fields, and the promoting effect of magnetic fields and magnetic nanoparticles on bone growth. In this study, a mouse model of osteoporosis was prepared by resection of bilateral ovaries; magnetic nanoparticles were injected into the paraventricular nucleus of the hypothalamus by stereotactic technique; and a rotating magnetic field was applied for one month. The bone mineral density of mice was measured using the MICRO-CT, and the cross-sectional structure of the left femur was obtained; the sera of the mice were obtained by enucleation of the eyeballs, and the levels of BALP and TRACP in the serum were detected.Group C: Sham-operated mice. Group o: Ovariectomized mice. Group on: Ovariectomy, followed by injection of magnetic nanoparticles into the paraventricular nucleus. Group onm: Ovariectomy, followed by injection of magnetic nanoparticles into the paraventricular nucleus, and then through the rotating magnetic field.The o group showed significant bone loss, CT value was significantly lower than that of the c group (Plt;0.001); serum BALP and TRACP levels were significantly lower than the c group (Plt;0.05), and the main manifestation was a significant reduction in bone formation (Plt; 0.001).The on group showed weaker bone loss, the CT value was significantly lower (Plt;0.001); serum BALP level was significantly higher than the o group (Plt;0.001); TRACP level and o group had no significant difference between but significantly lower than the c group ( Plt;0.05).The onm group showed an increase in osteogenesis, CT values were significantly higher than those of the o group and the on group (Plt;0.01); serum BALP levels were significantly higher than the o group and the on group (Plt;0.001), and the TRACP level was higher than that of the o group and on group (Plt;0.05). These data confirm the success of modeling in osteoporotic mice, demonstrating that injecting magnetic nanoparticles into the paraventricular nucleus of mice and subsequent addition of a rotating magnetic field can increase bone metabolic activity and play a role in promoting bone formation and bone remodeling positive effects. The results of the experimental studies confirm the role of magnetic stimulation in regulating bone metabolism and suggest that oxytocin may have a positive therapeutic effect on osteoporosis.

KEY WORDS:Osteoporosis, Oxytocin, Bone Metabolism, Magnetic Nanoparticles, Magnetic Field

目录

摘要 I

Abstract II

第一章 绪论 1

1.1 研究背景 1

1.1.1 骨质疏松症 1

1.1.2 骨的代谢调节 1

1.2 催产素 2

1.2.1 简介 2

1.2.2 催产素与骨代谢 3

1.3 磁性纳米颗粒 4

1.3.1 磁性纳米颗粒的特性 4

1.3.2 磁性纳米颗粒的应用 5

1.3.3 复合磁性纳米材料对骨的影响 5

1.3.4 磁场调控骨代谢 6

1.4 神经内分泌 6

1.4.1 神经内分泌与骨质疏松 6

1.4.2 磁场调控神经内分泌 7

1.5 研究目的 7

第二章 研究方法 8

2.1 实验器材 8

2.1.1 实验材料 8

2.1.2 实验仪器 8

2.2 实验操作 8

2.2.1 骨质疏松小鼠造模 9

2.2.2 脑室旁核立体定位注射磁性纳米颗粒 10

2.2.3 磁场作用 12

2.3 检测方法 13

2.3.1 核磁共振检测 13

2.3.2 Micro-CT测骨密度 13

2.3.3 测血清内标志物 14

第三章 结果与讨论 15

3.1 室旁核磁性纳米颗粒注射预实验 15

3.1.1 脑部核磁检测 15

3.1.2 催产素含量检测 16

3.2 骨质疏松小鼠造模检测 17

3.2.1 股骨横断面结构差异 17

3.2.2 腰椎骨骨密度差异 18

3.2.3 血清内成骨标志物BALP和破骨标志物TRACP 19

3.3 室旁核磁刺激对骨代谢的影响 21

3.3.1 股骨横断面结构差异 21

3.3.2 骨骨密度差异 24

3.3.3 血清内成骨标志物BALP和破骨标志物TRACP 25

第四章 总结 29

致谢 31

参考文献 32

绪论

骨质疏松与骨代谢

骨质疏松症

当下，骨质疏松症（osteoporosis, OP）已经成为世界性的公共卫生问题，在各种疾病中骨质疏松症作为一种日常常见病，发病率越来越高，表现出了当代中老年人的骨健康日益降低的现状，也已引起了世界各国的关注，成为当今的研究热点。中国作为一个人口大国，人口数总约达14亿，约占世界人口的18%，随着社会逐步进入老龄化，我国现在已经成为世界上骨质疏松患者最多的国家。据统计，我国50岁以上老年人中骨质疏松发病率约为15.7%。其中，妇女患病率较高，50-60岁年龄段妇女中患骨质疏松症约占30%，60岁以上的妇女约有30%-50%患病，中老年男性的骨质疏松患病率约为20%-30%。

骨质疏松症是一种由多种原因诱发的常见病，具体表现为骨密度和骨质量减少、骨组织结构受到破坏，进而表现为骨强度减弱，骨易脆、易骨折的全身性疾病。骨质疏松症因病因特点不同，可分为绝经后骨质疏松症、老年性骨质疏松症和特发性骨质疏松症。主要的患病人群包括绝经后妇女、70岁以后的老人和部分特殊青少年。病人患病后常出现腰背疼痛、身长缩短、呼吸功能下降、脊柱变形和脆性骨折等症状，继发性骨质疏松病人可能还同时伴有甲状腺亢奋、糖尿病等表现病症。患病后病人的生活活动受限，生活质量受损，甚至可能因骨折而造成死亡，这不仅对病人带来严重的生理和心理危害，也给家庭和社会带来沉重的负担。

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