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光照促渗增强皮肤光透明效果及机制研究

发布时间:2018-08-01 08:09
【摘要】:皮肤既是光诊疗的靶器官之一,也是实施活体光学成像的第一道屏障,这是因为皮肤的高散射限制光在组织的穿透深度。皮肤光透明技术的提出有望克服这一障碍,即向真皮引入一种高折射率、高渗透性的化学试剂,使得皮肤中有形成分与无形成分之间的折射率匹配,从而降低组织对光的散射,使得光在皮肤中的穿透深度增加。但该技术在活体应用中却面临着:皮肤角质层的天然阻挡作用限制光透明剂向真皮中的渗透。为此,多种物理、化学或物化方法用于促进光透明剂的透皮,但是多具有侵入性。 本文主要工作正是围绕如何提高光透明剂向皮肤中的渗透以提高皮肤光透明效果、及相关机制而展开的。主要研究内容及成果如下: 1)光照促渗增强皮肤光透明效果的比较研究:利用不同种类、不同波长、不同输出模式、不同照射剂量的光源照射皮肤,再涂抹光透明剂,观测皮肤反射谱的变化以评定皮肤光透明效果。研究表明,合适的光照均能在一定程度增加皮肤光透明效果,其中1064nm-Nd:YAG激光(两种不同输出模式:调Q和长脉宽模式)照射所致效果最优,且不会对皮肤表面产生肉眼可见的损伤。进一步,利用组织光谱测量方法对皮肤光透明前后的光学参数的变化进行测量,发现激光促进光透明剂渗透能显著降低皮肤对光的散射、增加光在皮肤中的穿透深度。 2)1064nm-Nd:YAG激光促渗增强皮肤光透明的机制研究:利用红外热像仪成像、组织切片HE染色以及双光子成像对1064nm-Nd:YAG激光照射所致皮肤表面温度、角质层微结构以及成份等展开研究。发现长脉宽Nd:YAG激光照射具有明显的光热效应,导致角质细胞温和剥脱和疏松,角蛋白自发荧光明显减弱,干扰角质层的正常屏障作用;而调Q-Nd:YAG激光照射具有典型的光机械作用,导致皮肤角质层形成微孔,完全破坏角质层细胞。皮肤角质层微结构的改变在至少一周内对皮肤光透明效果有持续的促进作用。 3)皮肤光透明机制:温升对皮肤光透明的影响:前一章研究发现激光产生的热效应能增强皮肤光透明效果,本章进一步研究了温度变化对皮肤光透明效果的影响。不同温度(4,25,32和45℃)的甘油被用于离体和在体研究。结果表明:相比较而言,以低于皮肤温度的甘油作用(4和25℃),皮肤光透明效果十分有限;以高于皮肤温度的甘油作用,能快速、显著地改善皮肤光透明效果,且甘油温度越高,皮肤光透明效果越好、速率越快。这说明温升确实能影响皮肤光透明效果。但在体皮肤光透明应用应低于皮肤耐受温度。 4)皮肤光透明技术提高激光祛除纹身效果的初步研究:建立纹身动物模型,在纹身区域涂抹37℃光透明剂后再利用1064nm-Nd:YAG激光(调Q)进行治疗,利用皮肤测试仪(MPA580, Maxemeter18probe)测量色素变化。通过比较联合治疗区域与单纯激光治疗区域纹身色素的变化,发现皮肤光透明剂的使用能够显著提高1064nm调Q-Nd:YAG激光清除蓝黑色纹身的效果,色素清除率提高约1.5倍;实验结果与蒙特卡洛(Monte Carlo)模拟的理论预测一致。因此,皮肤光透明能改善光在组织中传输的靶向性,提高到达深层纹身部位的有效光子数,从而有助于纹身色素的崩解和清除。
[Abstract]:Skin is not only one of the target organs of optical diagnosis and treatment, but also the first barrier to implement the optical imaging of living body. This is because the high scattering of skin restricts the penetrating depth of light in the tissue. The proposed skin transparency technique is expected to overcome this obstacle, that is, introducing a high refractive index, high permeability chemical reagent to the dermis, making the skin formed. The refractive index is matched with the invisible component, which reduces the scattering of light by tissue and increases the penetration depth of light in the skin. But in living applications, the technique faces the natural barrier of the skin cuticles to limit the penetration of transparent agents into the dermis. For this reason, a variety of physical, chemical or physical methods are used to promote light. Transparent agent transdermal, but more intrusive.
The main work of this paper is how to improve the penetration of transparent agents to the skin to improve the transparent effect of skin, and the related mechanisms. The main research contents and results are as follows:
1) a comparative study on the effect of light transparency and enhancement of light transparency: using different kinds, different wavelengths, different output modes, different irradiation doses of light source irradiated skin, and then smearing light transparent agent, observing the changes of skin reflection spectrum to evaluate the transparent effect of skin light. The effect of 1064nm-Nd:YAG laser (two different output modes: Q and long pulse width mode) is the best result, and it can not produce visible damage to the skin surface. Further, the changes of optical parameters before and after light transparency of skin are measured by tissue spectrometric method, and it is found that laser promotes light transparency. Osmotic energy can significantly reduce the light scattering from skin and increase the penetration depth of light in the skin.
2) study on the mechanism of 1064nm-Nd:YAG laser enhancement of skin transparency: infrared thermograph imaging, tissue section HE staining and two-photon imaging of skin surface temperature caused by 1064nm-Nd:YAG laser irradiation, cuticle microstructure and composition, etc., it is found that long pulse width Nd:YAG laser irradiation has obvious photothermal effect. The keratinocytes are mild exfoliation and looseness, and the spontaneous fluorescence of keratin decreases obviously and interferes with the normal barrier of the cuticle, while the Q-Nd:YAG laser irradiation has a typical photo mechanical effect, which causes the cuticle formation to form micropores and completely destroy the cuticle cells. The changes of the skin cuticle microstructures are transparent to the skin in at least a week. The effect has a continuous promotion.
3) skin transparency mechanism: the effect of temperature rise on the light transparency of the skin: the previous chapter found that the thermal effect produced by the laser can enhance the transparency effect of the skin. This chapter further studies the effect of temperature change on the transparent effect of skin. The glycerol at different temperatures (4,25,32 and 45 C) is used in vitro and in vivo. The results show that: In comparison with the glycerol action below the skin temperature (4 and 25 C), the light transparency effect of the skin is very limited; the effect of glycerol, which is higher than the skin temperature, can rapidly and significantly improve the transparency effect of the skin, and the higher the glycerol temperature, the better the transparent effect of the skin, the faster the rate is, but the temperature rise does affect the transparent effect of the skin. The transparent application of skin should be lower than that of skin.
4) a preliminary study of skin light transparent technology to improve the effect of laser removal of tattoos: establishing a tattoo animal model, using a transparent agent of 37 C in the tattoo area and then using 1064nm-Nd:YAG laser (Q) for treatment, and using MPA580 (Maxemeter18probe) to measure the change of pigment. The change of the tattoo pigment in the treatment area shows that the use of light transparent agent in the skin can significantly improve the effect of 1064nm Q-Nd:YAG laser removal of blue black tattoo, and the pigment removal rate increases about 1.5 times; the experimental results are consistent with the theoretical prediction of Monte Carlo (Monte Carlo) simulation. Therefore, the transparent skin of the skin can improve the target of light transmission in tissue. Sex, improve the number of effective photons reaching deep tattoos, thus contributing to the disintegration and removal of tattoo pigments.
【学位授予单位】:华中科技大学
【学位级别】:博士
【学位授予年份】:2014
【分类号】:R318.51

【参考文献】

相关期刊论文 前2条

1 毛宗珍;韩珍珍;朱(艹丹);;噻酮提高在体大鼠皮肤光透明效果的实验研究[J];光学学报;2009年07期

2 秦梅香,朱菁;调Q激光去除纹身[J];应用激光;2001年02期



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