慢性应激诱导小鼠毛发颜色改变及其机制的研究

发布时间：2019-03-30 20:32

【摘要】：随着科技的发展和生活节奏的加快,人们受到越来越复杂、越来越强烈的应激。应激已经成为人们生活中不可避免的因素。人们受到来自环境的应激时,机体会发生神经内分泌、细胞体液和心理等一系列变化。机体的适当反应有利于提高人们对环境的应对能力,而反应过度则会打破机体内环境的稳态甚至引起疾病。我国有关于“伍子胥过韶关,一夜愁白头”的传说。现代社会观察和调查也表明,应激和毛发颜色可能存在一定关联[1-3]。但是,目前尚无明确的实验研究证明应激可以导致毛发颜色改变。为了探究慢性应激和毛发颜色的关系及其机制,本研究从以下三方面进行了实验：实验设计：1、对C57BL/6小鼠进行为期90天的足底电刺击和束缚应激,构建慢性应激模型,观察小鼠毛发颜色改变情况,探究应激对小鼠毛发颜色的影响；2、检测小鼠皮肤黑色素含量、酪氨酸酶活性和毛囊黑色素细胞数量等与黑色素合成密切相关的指标,明确慢性应激对毛囊合成黑色素的影响：3、检测小鼠皮肤的炎症反应(包括皮肤炎性细胞浸润情况,NF-κB信号转导通路激活情况,IL-1β、IL-6和TNF-α等促炎细胞因子含量)并筛选变化显著的炎症因子；通过用含不同浓度TNF-α的培养基培养B16F10黑色素瘤细胞,检测其对黑色素合成的影响,探究应激诱导小鼠毛色改变的炎症机制。实验结果：1、慢性应激诱导小鼠毛发由黑色变为棕色；2、慢性应激诱导小鼠皮肤黑色素含量和酪氨酸酶活性下降,并引起毛囊黑色素细胞数量减少,慢性应激小鼠皮肤表皮出现不连续的黑色斑块；3、慢性应激诱导小鼠皮肤NF-κB细胞信号转导通路激活,皮肤IL-1p和IL-6水平呈升高趋势、TNF-α水平极显著升高,但是慢性应激小鼠皮肤中不存在炎症细胞浸润；TNF-α可以降低B16F10黑色素瘤细胞内酪氨酸酶活性并减少黑色素表达。实验结论：一方面,小鼠受到慢性应激后,皮肤NF-κB信号转导通路激活,TNF-α水平极显著升高,皮肤TNF-α水平的升高抑制小鼠毛囊黑色素细胞酪氨酸酶活性,酪氨酸酶酶活性的降低导致小鼠毛发颜色改变；另一方面,小鼠受到慢性应激后,可能存在毛囊黑色素干细胞向皮肤表皮的转移。该转移导致毛囊黑色素细胞数量减少,黑色素合成能力下降,导致小鼠毛发颜色改变。本研究首次明确了慢性应激和毛发颜色的关系,并初步阐释了其分子机制,为白发(特别是压力所致的白发)的防治提供了实验依据。
[Abstract]:With the development of science and technology and the acceleration of the pace of life, people are subjected to more and more complex, more and more intense stress. Stress has become an inevitable factor in people's lives. When people are subjected to environmental stress, neuroendocrine, cellular humoral and psychological changes occur. The proper response of the organism is helpful to improve people's ability to respond to the environment, and the overreaction will break the homeostasis of the environment and even cause the disease. Our country has the legend about Wu Zixu passing Shaoguan, one night worried white head. Modern social observation and investigation also showed that stress and hair color may be related to some extent [1]. However, there is no clear experimental study to prove that stress can lead to hair color change. In order to explore the relationship between chronic stress and hair color and its mechanism, the following three aspects were studied in this study: 1. C57BL/6 mice were subjected to electric stinging and restraint stress for 90 days to construct chronic stress model. To observe the change of hair color in mice and to explore the effect of stress on the hair color of mice. 2. To detect the melanin content, tyrosinase activity and melanocyte number in mouse skin, which are closely related to melanin synthesis, to determine the effect of chronic stress on melanin synthesis in hair follicles: 3, The inflammatory reaction (including the infiltration of skin inflammatory cells, activation of NF- 魏 B signal transduction pathway, the content of pro inflammatory cytokines such as IL-1 尾, IL-6 and TNF- 伪) was detected and the significantly changed inflammatory factors were screened. B16F10 melanoma cells were cultured in medium containing different concentrations of TNF- 伪, and their effects on melanin synthesis were detected to explore the inflammatory mechanism of hair color changes induced by stress in mice. The results were as follows: (1) chronic stress induced the hair of mice to change from black to brown; 2. Chronic stress induced the decrease of melanin content and tyrosinase activity in the skin of mice, and the decrease of melanocytes in hair follicles, and the discontinuous black plaques appeared in the skin epidermis of chronic stress mice. (3) chronic stress induced activation of NF- 魏 B cell signal transduction pathway, the levels of IL-1p, IL-6 and TNF- 伪 increased significantly in the skin of mice, but there was no infiltration of inflammatory cells in the skin of chronic stress mice. TNF- 伪 decreased tyrosinase activity and melanin expression in B16F10 melanoma cells. Conclusion: on the one hand, after chronic stress, the NF- 魏 B signal transduction pathway was activated and the level of TNF- 伪 was significantly increased. The elevated level of TNF- 伪 inhibited the tyrosinase activity of melanocytes in mouse hair follicles. The decrease of tyrosinase activity resulted in the change of hair color in mice. On the other hand, hair follicle melanin stem cells may be transferred to skin epidermis after chronic stress in mice. The transfer resulted in a decrease in the number of melanocytes in hair follicles, a decrease in melanin synthesis, and a change in hair color in mice. This study for the first time clarified the relationship between chronic stress and hair color, and preliminarily explained its molecular mechanism, which provided experimental basis for the prevention and treatment of white hair (especially the white hair caused by stress).
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.5

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