探讨维生素D代谢通路在斑秃外周血的表达及临床意义

发布时间：2018-07-26 11:52

【摘要】：研究背景维生素D是一种脂溶性类固醇化合物,能调节体内钙磷代谢,影响骨骼健康。可通过食物摄取,大部分由皮肤吸收UVB(Ultraviolet B)的照射,从7-脱氢胆固醇转化而来,前体维生素D_3于肝脏在25-羟化酶的催化下转化为25(OH)D_3,结合维生素D结合蛋白(Vitamin D Binding Protein)运输至肾脏,25(OH)D_3在1-a羟化酶的催化下形成1,25(OH)2D_3,后者与维生素D受体(Vitamin D Receptor,VDR)结合,发挥相应的生物功能。[1]近年来越来越多学者研究维生素D与自身免疫性疾病的相关性,已发现维生素D的缺乏与系统性红斑狼疮[2]、银屑病[3]、多发性硬化[4]等自身免疫性疾病有关;进而研究维生素D参与自身免疫性疾病发病的可能机制,已有体内外实验指出维生素D可能通过直接或间接地调控T淋巴细胞分化及细胞因子分泌,调节免疫反应。斑秃(Alopecia Areata,AA)为突发性边界清晰的圆形斑状脱发,发病机制尚不清楚。目前关于斑秃发病有多种学说,包括黑素细胞源性自身抗原的释放、免疫豁免状态的解除和调节性T细胞异常学说等,但现有研究多倾向认为斑秃是遗传易感性的基础上,环境因素作用于免疫系统产生的一种T细胞介导的针对生长期毛囊Th1型反应为特征的器官特异性自身免疫性疾病[5]。国内外有报道指出25(OH)D在斑秃患者外周血中低表达,亦有个别报道指出VDR在斑秃患者血清及头皮低表达。目前未见DBP及1-a羟化酶与斑秃相关性的研究,亦未见维生素D代谢通路与斑秃的相关性的研究。目的通过检测斑秃患者中外周血维生素D代谢通路(25(OH)D_3、1-a羟化酶、DBP、VDR)的表达量,初步探讨其与斑秃的相关性,探索斑秃的发病机制,为斑秃治疗提供新的靶点。方法采用酶联免疫吸附试验法(ELISA)检测44例斑秃患者血清中25(OH)D_3、1-a羟化酶、DBP、VDR水平,与44例健康体检者对照,并比较其在不同严重程度、不同病程、病情活动与否及初发与否的斑秃患者之间的差异。结果(1)斑秃组外周血的25(OH)D_3(27.41±11.18ng/ml)水平低于正常对照组(33.57±6.51 ng/ml),差异有统计学意义(p0.05);1-a羟化酶(4.66±1.40 ng/ml)、VDR(15.91±3.79 ng/ml)、DBP(27.86±5.06 ng/ml)水平均高于正常对照组(1.95±0.44 ng/ml,8.72±1.66 ng/ml,12.32±3.26 ng/ml),差异均有统计学意义。(p均0.05)。(2)斑秃组外周血25(OH)D_3水平与病情的关系:≤1年(27.87±11.49 ng/ml)和1年组(26.16±10.63 ng/ml)、轻型(25.68±11.83 ng/ml和重型斑秃组(28.60±10.78 ng/ml)、活动期(25.17±11.88 ng/ml)和非活动期组(29.36±9.17 ng/ml)、初发组(23.83±6.96 ng/ml)和复发组(29.25±12.54 ng/ml)的外周血25(OH)D水平无统计学差异(p均0.05)。(3)斑秃组外周血1-a羟化酶水平与病情的关系:≤1年组(5.26±1.29 ng/ml)外周血1-a羟化酶水平高于1年组(4.17±1.32 ng/ml),差异有统计学意义(p0.05);轻型(4.17±1.32 ng/ml)和重型斑秃组(4.52±1.32 ng/ml)、活动期(4.67±1.15 ng/ml)和非活动期组(5.27±1.29 ng/ml)、初发(5.12±1.41 ng/ml)和复发组(4.43±1.36 ng/ml)的外周血1-a羟化酶水平无统计学差异(p均0.05)。(4)斑秃组外周血VDR水平与病情的关系:≤1年(16.41±3.81 ng/ml)和1年组(15.50±3.80 ng/ml)、轻型(15.32±3.51 ng/ml)和重型斑秃组(16.32±3.40 ng/ml)、活动期(15.60±3.84 ng/ml)和非活动期组(18.05±3.93 ng/ml)、初发(15.42±3.30 ng/ml)和复发组(16.17±4.05 ng/ml)的外周血VDR水平无统计学差异(p0.05)。(5)斑秃组外周血DBP水平与病情的关系:活动期组(4.67±1.15 ng/ml)外周血DBP水平高于非活动期组(24.26±4.39 ng/ml),差异有统计学意义(p0.05);≤1年(28.55±5.39 ng/ml)和1年组(27.29±4.82 ng/ml)、轻型(26.79±5.69 ng/ml)和重型斑秃组(28.60±4.55 ng/ml)、初发(28.80±5.30 ng/ml)和复发组(27.38±4.96 ng/ml)的外周血DBP水平无统计学差异(p0.05)。结论(1)维生素D代谢通路中25(OH)D_3、1-a羟化酶、DBP、VDR可能参与了斑秃的发病;(2)外周血1-a羟化酶水平降低与斑秃的迁延相关;(3)外周血DBP水平与斑秃的活动性有相关性。
[Abstract]:Background vitamin D is a fat soluble steroid compound that regulates calcium and phosphorus metabolism in the body and affects bone health. Through food intake, most of the vitamin UVB (Ultraviolet B) is absorbed by the skin to transform from 7- dehydrogenase cholesterol. The precursor of vitamin D_3 is converted to 25 (OH) D_3 in the liver under the catalysis of 25- hydroxylase, combined with vitamin C. The D binding protein (Vitamin D Binding Protein) is transported to the kidney, and 25 (OH) D_3 forms 1,25 (OH) 2D_3 under the catalysis of 1-A hydroxylase. The latter combines with the vitamin D receptor and plays the corresponding biological function. The lack of D is associated with autoimmune diseases such as systemic lupus erythematosus [2], psoriasis [3] and multiple sclerosis [4], and then studies the possible mechanism of vitamin D involved in the pathogenesis of autoimmune diseases. In vivo and in vivo experiments have indicated that vitamin D may regulate the differentiation of T lymphocytes and cytokine secretion by direct or indirect regulation of vitamin D and regulate immunity. The pathogenesis of alopecia areata (Alopecia Areata, AA) is not clear. There are many theories about the pathogenesis of alopecia areata, including the release of melanocyte derived autoantigen, the release of immunity immunity and the regulation of the abnormal T cell theory. However, the current research tends to think that alopecia areata is hereditary On the basis of susceptibility, environmental factors play a role in an immune system produced by a T cell mediated organ specific autoimmune disease characterized by Th1 type reaction in the growth period of hair follicles. There are reports of low expression of 25 (OH) D in peripheral blood of alopecia alopecia, and some reports indicate that VDR is low in serum and scalp in alopecia alopecia. There is no study on the correlation between DBP and 1-A hydroxylase and alopecia areata, and no correlation between vitamin D metabolic pathway and alopecia areata. Objective to detect the expression of vitamin D metabolic pathway (25 (OH) D_3,1-a hydroxylase, DBP, VDR) in patients with alopecia areata, and to explore the relationship between alopecia alopecia and alopecia alopecia, and explore the pathogenesis of alopecia areata In order to provide new targets for the treatment of alopecia areata, the enzyme linked immunosorbent assay (ELISA) was used to detect the levels of 25 (OH) D_3,1-a hydroxylase, DBP, VDR in 44 patients with alopecia areata, compared with 44 healthy subjects, and compared the difference between the patients with alopecia areata in different severity, different course of disease, disease activity or not and first occurrence of alopecia. (1) the level of 25 (OH) D_3 (27.41 + 11.18ng/ml) of peripheral blood in the alopecia alopecia group was lower than that of the normal control group (33.57 + 6.51 ng/ml), and the difference was statistically significant (P0.05); 1-A hydroxylase (4.66 + 1.40 ng/ml), VDR (15.91 + 3.79 ng/ml), DBP (27.86 + 5.06 ng/ml) water were higher than that of normal control group (1.95 + 0.44 ng/ml, 8.72 + 4.66) The difference was statistically significant. (P 0.05). (2) the relationship between the level of 25 (OH) D_3 of peripheral blood in the alopecia alopecia group and the condition of the disease: < 1 years (27.87 + 11.49 ng/ml) and 1 year group (26.16 + 10.63 ng/ml), light light (25.68 + 11.83 ng/ml and severe alopecia alopecia group (28.60 + 10.78 ng/ml), active period (27.87) ng/ml) and inactive phase group 96 ng/ml) and recurrent group (29.25 + 12.54 ng/ml) of peripheral blood 25 (OH) D level had no statistical difference (P 0.05). (3) the relationship between the level of 1-A hydroxylase in the peripheral blood of the alopecia group and the condition: the level of 1-A hydroxylase in the peripheral blood of the group (5.26 + 1.29 ng/ml) was higher than that of 1 years group (4.17 + 1.32 ng/ml), and the difference was statistically significant (P0.05); and light (4.17 + ng/ml) and Severe alopecia areata (4.52 + 1.32 ng/ml), active period (4.67 + 1.15 ng/ml) and inactive phase group (5.27 + 1.29 ng/ml), primary (5.12 + 1.41 ng/ml) and recurrent group (4.43 + 1.36 ng/ml) of peripheral blood 1-A hydroxylase level had no statistical difference (P mean 0.05). (4) the relationship between the level of peripheral blood VDR in the alopecia alopecia group and the condition .50 + 3.80 ng/ml), light (15.32 + 3.51 ng/ml) and severe alopecia alopecia group (16.32 + 3.40 ng/ml), active phase (15.60 + 3.84 ng/ml) and inactive phase group (18.05 + 3.93 ng/ml), and there was no significant difference in peripheral blood VDR (P0.05) in the initial (15.42 + 3.30 ng/ml) and recurrent group (16.17 + 4.05 ng/ml). The relationship between the DBP level of peripheral blood in the alopecia alopecia group and the condition of the condition: The level of peripheral blood DBP in the active phase group (4.67 + 1.15 ng/ml) was higher than that in the inactive group (24.26 + 4.39 ng/ml), and the difference was statistically significant (P0.05); < 1 years > (28.55 + 5.39 ng/ml) and 1 year group (27.29 + 4.82 ng/ml); light (26.79 + 5.69 ng/ml) and severe alopecia alopecia group (28.60 + ng/ml). There was no statistical difference in DBP level in peripheral blood (P0.05). Conclusion (1) 25 (OH) D_3,1-a hydroxylase, DBP, VDR in vitamin D metabolic pathway may be involved in alopecia areata; (2) the decrease of 1-A hydroxylase in peripheral blood is associated with the deferment of alopecia alopecia; (3) the level of DBP in peripheral blood is associated with the activity of bald.
【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.71

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