探討維生素D代謝通路在斑禿外周血的表達(dá)及臨床意義
發(fā)布時(shí)間：2018-07-26 11:52
【摘要】：研究背景維生素D是一種脂溶性類固醇化合物,能調(diào)節(jié)體內(nèi)鈣磷代謝,影響骨骼健康�？赏ㄟ^(guò)食物攝取,大部分由皮膚吸收UVB(Ultraviolet B)的照射,從7-脫氫膽固醇轉(zhuǎn)化而來(lái),前體維生素D_3于肝臟在25-羥化酶的催化下轉(zhuǎn)化為25(OH)D_3,結(jié)合維生素D結(jié)合蛋白(Vitamin D Binding Protein)運(yùn)輸至腎臟,25(OH)D_3在1-a羥化酶的催化下形成1,25(OH)2D_3,后者與維生素D受體(Vitamin D Receptor,VDR)結(jié)合,發(fā)揮相應(yīng)的生物功能。[1]近年來(lái)越來(lái)越多學(xué)者研究維生素D與自身免疫性疾病的相關(guān)性,已發(fā)現(xiàn)維生素D的缺乏與系統(tǒng)性紅斑狼瘡[2]、銀屑病[3]、多發(fā)性硬化[4]等自身免疫性疾病有關(guān);進(jìn)而研究維生素D參與自身免疫性疾病發(fā)病的可能機(jī)制,已有體內(nèi)外實(shí)驗(yàn)指出維生素D可能通過(guò)直接或間接地調(diào)控T淋巴細(xì)胞分化及細(xì)胞因子分泌,調(diào)節(jié)免疫反應(yīng)。斑禿(Alopecia Areata,AA)為突發(fā)性邊界清晰的圓形斑狀脫發(fā),發(fā)病機(jī)制尚不清楚。目前關(guān)于斑禿發(fā)病有多種學(xué)說(shuō),包括黑素細(xì)胞源性自身抗原的釋放、免疫豁免狀態(tài)的解除和調(diào)節(jié)性T細(xì)胞異常學(xué)說(shuō)等,但現(xiàn)有研究多傾向認(rèn)為斑禿是遺傳易感性的基礎(chǔ)上,環(huán)境因素作用于免疫系統(tǒng)產(chǎn)生的一種T細(xì)胞介導(dǎo)的針對(duì)生長(zhǎng)期毛囊Th1型反應(yīng)為特征的器官特異性自身免疫性疾病[5]。國(guó)內(nèi)外有報(bào)道指出25(OH)D在斑禿患者外周血中低表達(dá),亦有個(gè)別報(bào)道指出VDR在斑禿患者血清及頭皮低表達(dá)。目前未見DBP及1-a羥化酶與斑禿相關(guān)性的研究,亦未見維生素D代謝通路與斑禿的相關(guān)性的研究。目的通過(guò)檢測(cè)斑禿患者中外周血維生素D代謝通路(25(OH)D_3、1-a羥化酶、DBP、VDR)的表達(dá)量,初步探討其與斑禿的相關(guān)性,探索斑禿的發(fā)病機(jī)制,為斑禿治療提供新的靶點(diǎn)。方法采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA)檢測(cè)44例斑禿患者血清中25(OH)D_3、1-a羥化酶、DBP、VDR水平,與44例健康體檢者對(duì)照,并比較其在不同嚴(yán)重程度、不同病程、病情活動(dòng)與否及初發(fā)與否的斑禿患者之間的差異。結(jié)果(1)斑禿組外周血的25(OH)D_3(27.41±11.18ng/ml)水平低于正常對(duì)照組(33.57±6.51 ng/ml),差異有統(tǒng)計(jì)學(xué)意義(p0.05);1-a羥化酶(4.66±1.40 ng/ml)、VDR(15.91±3.79 ng/ml)、DBP(27.86±5.06 ng/ml)水平均高于正常對(duì)照組(1.95±0.44 ng/ml,8.72±1.66 ng/ml,12.32±3.26 ng/ml),差異均有統(tǒng)計(jì)學(xué)意義。(p均0.05)。(2)斑禿組外周血25(OH)D_3水平與病情的關(guān)系:≤1年(27.87±11.49 ng/ml)和1年組(26.16±10.63 ng/ml)、輕型(25.68±11.83 ng/ml和重型斑禿組(28.60±10.78 ng/ml)、活動(dòng)期(25.17±11.88 ng/ml)和非活動(dòng)期組(29.36±9.17 ng/ml)、初發(fā)組(23.83±6.96 ng/ml)和復(fù)發(fā)組(29.25±12.54 ng/ml)的外周血25(OH)D水平無(wú)統(tǒng)計(jì)學(xué)差異(p均0.05)。(3)斑禿組外周血1-a羥化酶水平與病情的關(guān)系:≤1年組(5.26±1.29 ng/ml)外周血1-a羥化酶水平高于1年組(4.17±1.32 ng/ml),差異有統(tǒng)計(jì)學(xué)意義(p0.05);輕型(4.17±1.32 ng/ml)和重型斑禿組(4.52±1.32 ng/ml)、活動(dòng)期(4.67±1.15 ng/ml)和非活動(dòng)期組(5.27±1.29 ng/ml)、初發(fā)(5.12±1.41 ng/ml)和復(fù)發(fā)組(4.43±1.36 ng/ml)的外周血1-a羥化酶水平無(wú)統(tǒng)計(jì)學(xué)差異(p均0.05)。(4)斑禿組外周血VDR水平與病情的關(guān)系:≤1年(16.41±3.81 ng/ml)和1年組(15.50±3.80 ng/ml)、輕型(15.32±3.51 ng/ml)和重型斑禿組(16.32±3.40 ng/ml)、活動(dòng)期(15.60±3.84 ng/ml)和非活動(dòng)期組(18.05±3.93 ng/ml)、初發(fā)(15.42±3.30 ng/ml)和復(fù)發(fā)組(16.17±4.05 ng/ml)的外周血VDR水平無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。(5)斑禿組外周血DBP水平與病情的關(guān)系:活動(dòng)期組(4.67±1.15 ng/ml)外周血DBP水平高于非活動(dòng)期組(24.26±4.39 ng/ml),差異有統(tǒng)計(jì)學(xué)意義(p0.05);≤1年(28.55±5.39 ng/ml)和1年組(27.29±4.82 ng/ml)、輕型(26.79±5.69 ng/ml)和重型斑禿組(28.60±4.55 ng/ml)、初發(fā)(28.80±5.30 ng/ml)和復(fù)發(fā)組(27.38±4.96 ng/ml)的外周血DBP水平無(wú)統(tǒng)計(jì)學(xué)差異(p0.05)。結(jié)論(1)維生素D代謝通路中25(OH)D_3、1-a羥化酶、DBP、VDR可能參與了斑禿的發(fā)病;(2)外周血1-a羥化酶水平降低與斑禿的遷延相關(guān);(3)外周血DBP水平與斑禿的活動(dòng)性有相關(guān)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.
【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R758.71
本文編號(hào)：2145922
[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.
【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R758.71
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