【摘要】：目的:系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus,SLE)是一種以免疫性炎癥為突出表現(xiàn)的自身免疫性疾病。目前認(rèn)為SLE發(fā)病與環(huán)境、遺傳、激素水平及免疫異常等因素相關(guān),但具體機(jī)制尚未完全闡明。SLE患者體內(nèi)除產(chǎn)生大量自身抗體外,還存在免疫細(xì)胞、細(xì)胞因子等免疫異常。維生素D作為一種神經(jīng)-內(nèi)分泌-免疫調(diào)節(jié)激素,通過與特定的維生素D受體(vitamin D receptor,VDR)結(jié)合,對(duì)抗原呈遞細(xì)胞、T細(xì)胞、B細(xì)胞等免疫細(xì)胞發(fā)揮效應(yīng),調(diào)節(jié)免疫細(xì)胞的增殖與分化、炎癥因子及免疫球蛋白表達(dá)等。據(jù)報(bào)道維生素D不足與多種自身免疫性疾病相關(guān),如多發(fā)性硬化(multiplesclerosis,MS)、Ⅰ型糖尿病(type 1 diabetes mellitus,T1DM)、炎性腸病(Inflammatory Bowel Disease,IBD)、類風(fēng)濕關(guān)節(jié)炎(rheumatoid arthritis,RA)、SLE等。SLE患者普遍存在維生素D水平減低和淋巴細(xì)胞亞群異常。本研究通過檢測(cè)初發(fā)SLE患者及健康人的血清25(OH)D3及外周血淋巴細(xì)胞亞群,分析SLE患者25(OH)D3水平和淋巴細(xì)胞亞群的情況,并探討25(OH)D3與淋巴細(xì)胞亞群的關(guān)系、臨床意義和兩者在SLE發(fā)病機(jī)制中的作用。方法:采用化學(xué)發(fā)光微粒子免疫檢測(cè)法檢測(cè)31例初發(fā)系統(tǒng)性紅斑狼瘡患者血清25-羥維生素D水平與21例健康對(duì)照組進(jìn)行比較。采用流式細(xì)胞術(shù)檢測(cè)31例初發(fā)系統(tǒng)性紅斑狼瘡患者外周血CD3+T細(xì)胞、CD3+CD4+Th細(xì)胞、CD3+CD8+Ts細(xì)胞、Th/Ts、CD19+B細(xì)胞及CD3-CD16+56+NK細(xì)胞百分率并與健康對(duì)照組進(jìn)行比較。對(duì)系統(tǒng)性紅斑狼瘡患者25-羥維生素D水平與系統(tǒng)性紅斑狼瘡疾病活動(dòng)指數(shù)(systemic lupus erythematosus disease activity index,SLEDAI)、淋巴細(xì)胞亞群進(jìn)行相關(guān)分析。結(jié)果:1 25(OH)D3在SLE組的水平低于對(duì)照組[(10.19±3.94)ng/ml]與[(14.11±3.62)ng/ml](t=-3.63,P0.05);2依據(jù)SLEDAI評(píng)分進(jìn)行分組,在非活動(dòng)組25(OH)D3水平與對(duì)照組無顯著差異[(12.46±3.25)ng/ml]與[(14.11±3.62)ng/ml](t=-1.50,P0.05),活動(dòng)組低于非活動(dòng)組[(7.05±2.39)ng/ml]與[(12.46±3.25)ng/ml](t=5.08,P0.05),活動(dòng)組低于對(duì)照組[(7.05±2.39)ng/ml]與[(14.11±3.62)ng/ml](t=-6.22,P0.05);3 SLE患者外周血CD3+T細(xì)胞百分率與對(duì)照組之間差異無統(tǒng)計(jì)學(xué)意義[(69.54±8.73)%]與[(71.31±6.33)%](t=-0.80,P0.05),SLE患者CD3+CD4+Th細(xì)胞百分率[(28.48±8.13)%]低于對(duì)照組[(40.64±5.04)%],差異有統(tǒng)計(jì)學(xué)意義(t=-6.10,P0.05)。SLE患者Th/Ts[0.80(0.50,1.03)]低于對(duì)照組[1.50(1.20,1.79)],差異有統(tǒng)計(jì)學(xué)意義(Z=-4.9,P0.05)。SLE患者CD3-CD16+56+NK細(xì)胞百分率[(5.77±3.17)%]低于對(duì)照組[(12.20±2.50)%],差異有統(tǒng)計(jì)學(xué)意義(t=-7.80,P0.05)。SLE患者CD3+CD8+Ts細(xì)胞百分率[(38.61±10.07)%]高于對(duì)照組[(28.62±4.51%)],差異有統(tǒng)計(jì)學(xué)意義(t=4.85,P0.05)。SLE患者CD19+B細(xì)胞[(19.70±7.90)%]高于對(duì)照組[(11.01±3.81)%],差異有統(tǒng)計(jì)學(xué)意義(t=5.28,P0.05);4非活動(dòng)組CD3+T細(xì)胞百分率[(71.82±7.85)%]與對(duì)照組[(71.31±6.33)%]之間差異無統(tǒng)計(jì)學(xué)意義(t=0.23,P0.05),非活動(dòng)組CD3+CD4+Th細(xì)胞百分率[(33.45±6.44)%]低于對(duì)照組[(40.65±5.04)%](t=-3.91,P0.05),非活動(dòng)組Th/Ts[1.01(0.75,1.18)]低于對(duì)照組[1.50(1.20,1.79)](Z=-3.73,P0.05),非活動(dòng)組CD3-CD16+56+NK細(xì)胞百分率[(5.07±2.89)%]低于對(duì)照組[(12.20±2.50)%](t=-8.26,P0.05),CD3+CD8+Ts細(xì)胞、CD19+B細(xì)胞百分率高于對(duì)照組[(35.12±8.02)%]與[(28.62±4.51)%](t=3.05,P0.05)和[(17.19±6.76)%]與[(11.01±3.81)%](t=3.58,P0.05);5活動(dòng)組CD3+T細(xì)胞百分率與對(duì)照組之間差異無統(tǒng)計(jì)學(xué)意義[(66.39±9.21)%]與[(71.31±6.33)%](t=-1.85,P0.05),活動(dòng)組CD3+CD4+Th細(xì)胞百分率[(21.59±4.26)%]低于對(duì)照組[(40.64±5.04)%](t=-3.91,P0.05),活動(dòng)組Th/Ts[0.49(0.39,0.70)]低于對(duì)照組[1.50(1.20,1.79)](Z=-4.63,P0.05),活動(dòng)組CD3-CD16+56+NK細(xì)胞百分率[(6.74±3.38)%]低于對(duì)照組[(12.20±2.50)%](t=-5.40,P0.05);CD3+CD8+Ts細(xì)胞、CD19+B細(xì)胞百分率高于對(duì)照組[(43.44±10.91)%]與[(28.62±4.51)%](t=4.66,P0.05)和[(23.17±8.29)%]與[(11.01±3.81)%)](t=4.97,P0.05);6活動(dòng)組與非活動(dòng)組CD3+T細(xì)胞百分率[(66.39±9.21)%]與[(71.82±7.85)%](t=1.77,P0.05)、CD3-CD16+56+NK細(xì)胞百分率[(6.74±3.38)%]與[(5.07±2.89)%](t=-1.48,P0.05)之間差異均無統(tǒng)計(jì)學(xué)意義,活動(dòng)組CD3+CD4+Th細(xì)胞百分率、Th/Ts均低于非活動(dòng)組[(21.59±4.26)%]與[(33.45±6.44)%](t=5.77,P0.05)、[0.49(0.39,0.70)]與[1.01(0.75,1.18)](Z=-3.39,P0.05),CD3+CD8+Ts細(xì)胞和CD19+B細(xì)胞百分率均高于非活動(dòng)組[(43.44±10.91)%]與[(35.12±8.02)%](t=-2.45,P0.05)、[(23.17±8.29)%]與[(17.19±6.76)%](t=-2.21,P0.05);7 SLE患者按Th/Ts比值分為兩組,倒置組25(OH)D3水平低于未倒置組[(9.07±3.94)ng/ml]與[(11.95±3.40)ng/ml](t=-2.09,P0.05);8 SLE組25(OH)D3水平與SLEDAI呈負(fù)相關(guān)(r=-0.545,P0.05),SLE組25(OH)D3水平與CD3+CD4+Th細(xì)胞百分率、Th/Ts正相關(guān)(r=0.456,P0.05)、(r=0.477,P0.05)。SLE組25(OH)D3水平與CD3+T細(xì)胞、CD3+CD8+Ts細(xì)胞、CD19+B細(xì)胞、CD3-CD16+56+NK細(xì)胞百分率均無相關(guān)性(P0.05)。結(jié)論:1 SLE患者存在25(OH)D3水平降低及淋巴細(xì)胞亞群異常,并可作為SLE患者疾病活動(dòng)的一項(xiàng)參考指標(biāo)。2 SLE患者血清25(OH)D3水平與淋巴細(xì)胞亞群CD3+CD4+Th細(xì)胞百分率、Th/Ts負(fù)相關(guān),維生素D可能與SLE發(fā)病有關(guān)。
[Abstract]:Objective: systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune inflammation. At present, it is believed that the pathogenesis of SLE is related to environment, heredity, hormone level and immune abnormality, but the specific mechanism has not yet fully demonstrated that there is still a large number of autoantibodies in the body of.SLE patients. Immune cells, cytokines, and other immune abnormalities. Vitamin D, as a neuroendocrine immunomodulatory hormone, is combined with a specific vitamin D receptor (vitamin D receptor, VDR) to antagonism immune cells, such as primary presenting cells, T cells, B cells, and other immune cells, regulating the proliferation and differentiation of immune cells, inflammatory factors and immunoglobulin It is reported that vitamin D deficiency is associated with a variety of autoimmune diseases, such as multiple sclerosis (multiplesclerosis, MS), type I diabetes (type 1 diabetes mellitus, T1DM), inflammatory bowel disease (Inflammatory Bowel Disease, IBD), rheumatoid arthritis (rheumatoid), and so on. This study analyzed the level of 25 (OH) D3 and lymphocyte subsets in patients with primary SLE and healthy human serum 25 (OH) D3 and peripheral blood lymphocyte subsets, and explored the relationship between 25 (OH) D3 and lymphocyte subsets, the clinical significance and the role of the two in the pathogenesis of SLE. The serum 25- hydroxyvitamin D levels of 31 patients with primary systemic lupus erythematosus were compared with that of 21 healthy controls. Flow cytometry was used to detect the peripheral blood CD3+T cells, CD3+CD4+Th cells, CD3+CD8 +Ts cells, Th/Ts, CD19+B cells and CD3-CD16+56+NK fine of 31 patients with primary systemic lupus erythematosus. The percentage of 25- hydroxyvitamin D in systemic lupus erythematosus patients and systemic lupus erythematosus disease activity index (systemic lupus erythematosus disease activity index, SLEDAI) and lymphocyte subsets were analyzed. Results: 125 (OH) D3 in the SLE group was lower than that of the control group [(10.19 + 3.) 94) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-3.63, P0.05); 2 on the basis of SLEDAI score, there was no significant difference between the non active group 25 (OH) D3 and the control group [12.46 + 3.25) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-1.50, P0.05), and the active group was lower than the non active group [7.05 + 2.39) ng/ml] and [12.46 + 3.25). (7.05 + 2.39) ng/ml] and [(14.11 + 3.62) ng/ml] (t=-6.22, P0.05); the percentage of CD3+T cells in peripheral blood of patients with 3 SLE was not statistically significant [(69.54 + 8.73)%] and [(71.31 + 6.33)%] (t=-0.80, P0.05), and the percentage of CD3+CD4+Th cells in SLE patients [(28.48 + 8.13)%] was lower than that of the control group [(40.64 + 5.04)%], the difference was statistically significant The meaning (t=-6.10, P0.05).SLE patients Th/Ts[0.80 (0.50,1.03)] was lower than the control group [1.50 (1.20,1.79)], the difference was statistically significant (Z=-4.9, P0.05).SLE patients CD3-CD16+56+NK cell percentage [(5.77 + 3.17)%] was lower than the control group [(12.20 + 2.50)%], the difference was (38.61 + 10.07) (38.61 + 10.07). Higher than the control group [(28.62 + 4.51%)], the difference was statistically significant ((t=4.85, P0.05).SLE patients CD19+B cells [(19.70 + 7.90)%] higher than the control group [(11.01 + 3.81)%], the difference was statistically significant (t=5.28, P0.05); 4 non active group CD3+T cell percentage [(71.82 + 7.85)%] and the control group [(71.31 + 6.33)%] difference was not statistically significant (t=0.23, P0.) 05) the percentage of CD3+CD4+Th cells in the inactive group [(33.45 + 6.44)%] was lower than that of the control group [(40.65 + 5.04)%] (t=-3.91, P0.05), the non active group Th/Ts[1.01 (0.75,1.18)] was lower than the control group [1.50 (1.20,1.79)] (Z=-3.73, P0.05), the percentage of the non active group CD3-CD16+56+NK cells [(5.07 + 2.89)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-8.26, P0.05). The percentage of CD19+B cells was higher than that in the control group [(35.12 + 8.02)%] and [(28.62 + 4.51)%] (t=3.05, P0.05) and [(17.19 + 6.76)%] and [(11.01 + 3.81)%] (t=3.58, P0.05), and there was no statistical difference between the percentage of CD3+T cells in the active group and the control group [(66.39 + 9.21)%] and [(71.31 + 6.33)%] (t=-1.85, P0.05), and the percentage of CD3+CD4+Th cells in the active group. The rate [(21.59 + 4.26)%] was lower than that of the control group [(40.64 + 5.04)%] (t=-3.91, P0.05), Th/Ts[0.49 (0.39,0.70) in the active group was lower than the control group [1.50 (1.20,1.79)] (Z=-4.63, P0.05). The percentage of CD3-CD16+56+NK cells in the active group [(6.74 + 3.38)%] was lower than that of the control group [(12.20 + 2.50)%] (t=-5.40, P0.05), and the percentage of CD3+CD8+Ts cells was higher than that of the control group. (43.44 + 10.91)%] and [(28.62 + 4.51)%] (t=4.66, P0.05) and [(23.17 + 8.29)%] and [(11.01 + 3.81)%]] (t=4.97, P0.05); the percentage of CD3+T cells in the 6 active group and the inactive group [(66.39 + 9.21)%] and [(71.82 + 7.85)%] (t=1.77, P0.05), the percentage of CD3-CD16+ 56+NK cells [(6.74 +]%)] and [(t=-1.48, P0.05)] have no statistics The percentage of CD3+CD4+Th cells in the active group was lower than that in the non active group [(21.59 + 4.26)%] and [(33.45 + 6.44)%] (t=5.77, P0.05), [0.49 (0.39,0.70)] and [1.01 (0.75,1.18)] (Z=-3.39, P0.05), and the percentage of CD3+CD8+Ts cells and CD19+B cells were higher than those in the non active group [(43.44 + 10.91)%] and [35.12 + 8.02)%], [23.17 + 8.2]. 9)%] and [(17.19 + 6.76)%] (t=-2.21, P0.05); 7 SLE patients were divided into two groups according to the ratio of Th/Ts, and the level of 25 (OH) D3 in the inverted group was lower than that in the non inverted Group [9.07 + 3.94) ng/ml] and [11.95 + 3.40) ng/ml] (t=-2.09, P0.05), and the level of 25 (OH) was positively correlated with the percentage of cells. (r=0.456, P0.05), (r=0.477, P0.05).SLE group 25 (OH) D3 levels have no correlation with CD3+T cells, CD3+CD8+Ts cells, CD19+B cells, and CD3-CD16+56+NK cells (P0.05). Conclusion: there is a decrease in the level of 25 (1) and the abnormal lymphocyte subgroup, and can be used as a reference index for the disease activity of the patients. The level of D3 is negatively correlated with the percentage of CD3+CD4+Th lymphocyte and Th/Ts, and vitamin D may be related to the pathogenesis of SLE.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R593.241

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本文編號(hào)：2138485