摘要
催产素主要由下丘脑室旁核细胞合成与分泌，而后经过垂体后叶释放入外周血的一种神经内分泌激素，有着促进分娩和刺激哺乳的重要功能。并且随着催产素研究的深入，研究者更多地关注其对社交行为以及精神疾病的影响。本实验室长期研究的一种磁性纳米材料瑞存（Ferumoxytol），是一种多糖外壳包裹的超顺磁性氧化铁纳米粒子，有着良好的稳定性和生物相容性。我们将瑞存作为磁增强剂注射到小鼠室旁核，外加旋转磁场作用，纳米颗粒响应磁场在室旁核处形成局部增强的精准磁刺激，以此促进室旁核分泌催产素。然后，通过调节磁性纳米颗粒的注射浓度、注射量，以及旋转磁场的作用强度、作用时间、作用频率来调控催产素的分泌。此外，通过行为学实验探究此方法对小鼠社交能力的影响。具体工作如下： 首先，使用脑立体定位技术将磁性纳米颗粒注射到小鼠室旁核，对小鼠脑部进行磁共振成像（MRI），分别检测1周、2周、3周、4周的MRI图像，图像中室旁核位置的灰度值即对应磁性纳米颗粒的量。发现直至第4周，磁颗粒依然可以在小鼠室旁核位置稳定存在，且随时间的推移，磁性颗粒的量不断减少。此外，通过与正常小鼠MRI图像对比，注射磁性纳米颗粒小鼠并没有明显损伤炎症出血症状，脑切片病理染也未发现明显损伤情况，表明此方法比较安全。
接着，对注射小鼠进行旋转磁场作用，发现注射磁性纳米颗粒并施加磁场作用组小鼠与对照组相比催产
素水平有着显著性差异，而注射生理盐水以及只注射磁性纳米颗粒不加磁场作用组没有显著性差异，表明基于磁性纳米颗粒增强的磁刺激能够促进小鼠室旁核催产素的表达。在此基础上，通过调节瑞存的注射条件，发现随着注射浓度的增加，催产素水平不断增加，随着注射量的增加，催产素水平反而不断减少。然后通过调节旋转磁场的作用条件，发现随着磁场作用强度的增加，催产素水平不断增加，随着磁场作用时间的增加，催产素水平不断增加，而随着旋转磁场频率的变化，催产素水平没有明显变化。
最后，对注射小鼠使用磁场作用一周后，进行三箱社交行为实验，发现我们这种基于磁性纳米颗粒增强的神经磁刺激方法能够对小鼠社交能力产生一定的促进作用，进一步地，我们发现小鼠血液催产素水平与社交能力结果存在一定的相关性。
关键词：催产素，磁性纳米颗粒，旋转磁场，神经磁刺激，社交行为
Abstract
Oxytocin is a kind of neuroendocrine hormone, which is mainly synthesized and secreted by hypothalamic paraventricular nucleus (PVN) cells, and then released into the peripheral blood by the posterior pituitary gland. It has important functions of promoting childbirth and stimulating breastfeeding. And with the deepening of oxytocin research, researchers are paying more attention t
o their impact on social behavior and mental diseases. Ferumoxytol is a long-term research magnetic nanomaterial in our laboratory, it is a kind of superparamagnetic iron oxide (SPIO) nanoparticles coated with polysaccharide envelope, which has excellent stability and biocompatibility. We injected ferumoxytol as a magnetic enhancer into the PVN of the mouse, and exerted a rotating magnetic field. The nanoparticles responded to the magnetic field to form a locally enhanced magnetic stimulation at the PVN, thereby promoting the secretion of oxytocin from the PVN. Then, the secretion of oxytocin was regulated by adjusting the injection conditions of magnetic nanoparticles and the parameters of magnetic field. In addition, the effects of this method on the social ability of mice were explored through behavioral experiments. The specific work is as follows:
Firstly, the brain stereotactic technique was used to inject magnetic nanoparticles into the PVN of the mouse, and magnetic resonance imaging (MRI) was performed on the brain of the mouse to detect MRI images of 1 week, 2 weeks, 3 weeks, and 4 weeks, respectively. The blackness value of the position of the PVN corresponded to the amount of magnetic nanoparticles. It was found that until the fourth week, magnetic nanoparticles remained stable in the PVN of the mouse, and the amount of the magnetic nanoparticles continued to decrease over time. In addition, by contrast with normal mouse MRI images, the injected mice did not have significant injury symptoms including inflammation, bleeding, etc. These indicated that this method was safe.
Then, the injected mice were treated by the rotating magnetic field, and it was found that the mice which were injected magnetic nanoparticles and exerted magnetic field had significant differences in oxytocin level compared with the control group, while the mice injected physiological saline and the mice injected ferumoxytol but not exerted magnetic field did not have significant differences. It indicated that nanomaterial-enhanced magnetic stimulation promoted the expression of oxytocin in the PVN of mice. Based on this, by adjusting the injection conditions of magnetic nanoparticles, it was found that the oxytocin level increased with the increase of the injection concentration, and the oxytocin level decreased with the increase of the injection volume. Then, by adjusting the parameters of the rotating magnetic field, it was found that the oxytocin level increased with the increase of the magnetic field intensity, the oxytocin level increased with the increase of the magnetic field stimulation time,
and the oxytocin level did not change significantly with the increase of frequency.
Finally, after using magnetic fields in the injected mice, 3-chambered social test was carried out. It was found that our magnetic nanoparticle-enhanced neuromagnetic stimulation method can promote the social ability of mice. Further, we found that there is a certain correlation between blood oxytocin levels and the social ability.
Keywords:oxytocin, magnetic nanoparticles, rotating magnetic field, nerve magnetic stimulation, sociality
目录
摘要............................................................................................................................................. II 第一章绪论 (1)
1.1引言 (1)
1.2 催产素 (1)
1.2.1 催产素的合成与分泌 (2)
1.2.2 催产素的作用 (2)
1.2.3 催产素的外周和中枢效应 (3)
1.2.4 催产素对社交行为的影响 (4)
1.3 神经刺激技术 (5)
1.3.1 神经刺激技术的主要类型 (6)
水暖炉
1.3.2 神经刺激与内分泌的潜在联系 (6)
1.4 医用磁性纳米材料 (7)
1.4.1 磁性氧化铁纳米材料的优良特性 (7)
车载mp3播放器1.4.2 磁性氧化铁纳米材料在生物医学领域的应用 (8)
1.4.3 磁性氧化铁纳米材料在磁共振成像中的应用 (9)
1.4.4 基于磁性氧化铁纳米颗粒增强的深部磁刺激 (10)
1.5 论文主要工作 (11)
伸缩杆第二章脑定位注射安全性探究以及磁性纳米颗粒在室旁核示踪 (13)
2.1 引言 (13)
2.2 实验材料、仪器 (14)
2.2.1 实验材料 (14)
2.2.2 实验仪器 (14)
2.3 实验方法 (15)
2.3.1 玻璃针头的拉制 (15)
2.3.2 玻璃显微注射针的制作 (15)
2.3.3 小鼠室旁核脑立体定位注射磁性纳米颗粒 (16)
2.3.4 磁共振检测小鼠头部 (17)
2.3.5 小鼠灌注取脑 (18)
2.3.6 小鼠脑组织切片病理染 (18)
2.4 实验结果与讨论 (19)
电子发声挂图2.4.1 玻璃显微注射针的改良 (19)
2.4.2 磁共振成像检测脑定位注射的损伤情况 (20)
2.4.3 小鼠脑组织切片病理染判断脑定位注射损伤情况 (22)
2.4.4 磁性纳米颗粒在小鼠室旁核示踪 (23)
app监测2.5 本章小结 (25)
第三章磁性纳米颗粒增强的磁刺激对小鼠室旁核催产素分泌的调节研究 (27)
3.1 引言 (27)
3.2 实验材料、仪器 (27)
3.2.1 实验材料 (27)
3.2.2 实验仪器 (28)
3.3 实验方法 (29)
3.3.1 小鼠室旁核脑定位注射磁性纳米颗粒 (29)
3.3.2 旋转磁场作用小鼠 (30)
3.3.3 小鼠眼球取血 (31)
3.3.4 分离血清 (31)
3.3.5 酶联免疫吸附检测 (31)
3.4 实验结果与讨论 (32)
3.4.1 磁性纳米颗粒增强的磁刺激对小鼠催产素水平的影响 (32)
3.4.2 磁性纳米颗粒注射的条件对催产素分泌的调节作用 (34)
3.4.3 磁场作用条件对催产素分泌的调节作用 (36)
3.4.4 磁性纳米颗粒增强的磁刺激对小鼠加压素水平的影响 (39)
3.5 本章小结 (40)
第四章磁性纳米颗粒增强的神经磁刺激对小鼠社交行为的影响 (43)
4.1 引言 (43)
4.2 实验材料、仪器 (43)
4.2.1 实验材料 (43)
4.2.2 实验仪器 (44)
4.3 实验方法 (44)
4.3.1 小鼠室旁核脑定位注射磁性纳米颗粒 (44)
4.3.2 旋转磁场作用小鼠 (45)
4.3.3 小鼠三箱社交行为实验 (45)
路障灯4.4 实验结果与讨论 (47)
4.4.1 小鼠三箱社交行为实验 (47)
4.4.2 小鼠血液催产素水平检测 (50)
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