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抗中性粒细胞胞浆抗体相关性小血管炎患者血清炎性因子与visfatin的表达

发布时间:2018-07-26 15:34
【摘要】:目的:(1)探讨抗中性粒细胞胞浆抗体(ANCA)及其靶抗原蛋白酶3(PR3)和髓过氧化物酶(MPO)的检测对ANCA相关性小血管炎(AASV)的应用价值;(2)观察AASV患者在小血管炎症活动期,血清炎性因子C反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)和内脏脂肪素(visfatin)的浓度变化及缓解期走向;(3)分析主要由内脏脂肪分泌的visfatin在AASV炎性损伤和免疫调控方面的作用,及其与CRP、IL-6、TNF-α间的潜在关联。 方法:对52例AASV活动期与25例缓解期血清样本采用间接免疫荧光法检测ANCA,依据荧光显微镜下免疫荧光的着染部位不同分为胞浆型ANCA(cANCA)和核周型ANCA(pANCA);应用酶联免疫吸附法测量PR3、MPO、 IL-6、TNF-α及visfatin;免疫比浊法测定CRP含量。 结果:(1) cANCA与pANCA各自识别对应的靶抗原PR3和MPO,具有靶抗原特异性(P0.001),且较长时间内不随疾病的转归而改变(P0.05)。(2)AASV活动期CRP、IL-6、TNF-α、visfatin水平较正常对照组均升高(P0.001);活动期与缓解期比较CRP(P0.05)、IL-6(P0.001)含量不同程度下降;TNF-α没有明显降低(P0.05);而AASV缓解期visfatin含量较治疗前仍继续升高(P0.05)。缓解期与对照组比较CRP(P0.001)、TNF-α(P0.05)、visfatin(P0.001)仍有差异,但IL-6已接近正常对照组(P0.05)。(3) AASV患者各炎性因子间均呈正相关性,CRP与IL-6间的相关系数为0.471(P0.001), CRP与TNF-α间的相关系数为0.315(P0.05), CRP与visfatin间的相关系数为0.364(P0.01), IL-6与TNF-α司的相关系数性为0.458(P0.01), IL-6与visfatin间的相关系数为0.577(P0.001),TNF-α与visfatin间的相关系数为0.550(P0.001)。 结论:ANCA及其靶抗原PR3和MPO的检测具有重要的疾病诊断价值,但由于其在体内浓度维持时间较长,不能用ANCA及其靶抗原水平来预知血管炎的活动性、治疗效果、缓解和/或已经复发。数据显示,AASV活动期与对照组比较,血清炎性因子CRP、IL-6、 TNF-α和visfatin浓度显著升高,且各炎性因子和visfatin间存在正相关调控关系。在缓解期CRP、IL-6、出现不同程度的下调,而TNF-α含量回落不明显,缓解期血清visfatin的含量较活动期仍有所升高,提示visfatin和TNF-α之间存在互为调控的剂量依赖关系,visfatin的这一变化可能也预示着AASV这一慢性消耗性疾病在维持缓解期内脏脂肪细胞的缓慢修复,对延长患者的中性粒细胞的生存时间起作用。
[Abstract]:Objective: (1) to investigate the value of detection of anti-neutrophil cytoplasmic antibody (ANCA) and its target antigen protease 3 (PR3) and myeloperoxidase (MPO) in (AASV) of ANCA associated vasculitis. The changes of serum inflammatory factor C reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor 伪 (TNF- 伪) and visceral lipoprotein (visfatin) and the tendency of remission were analyzed. (3) the role of visfatin, mainly secreted by visceral fat, in the inflammatory injury and immune regulation of AASV was analyzed. And its potential association with CRP IL-6 TNF- 伪. Methods: the serum samples of 52 patients with active AASV and 25 patients with remission were detected by indirect immunofluorescence method. According to the location of immunofluorescence staining under fluorescence microscope, they were divided into cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA); using enzyme-linked immunosorbent assay (Elisa). The levels of PR3 MPO, IL 6 TNF- 伪 and visfatin were measured by immunoturbidimetric method. The content of CRP was determined by immunoturbidimetric method. Results: (1) cANCA and pANCA recognized the corresponding target antigens PR3 and MPO respectively, which had target antigen specificity (P0.001), and did not change with the outcome of the disease for a long time (P0.05). (2). The level of AASV IL-6TNF- 伪 visfatin in active phase of AASV was higher than that in normal control group (P0.001). The content of CRP (P0.05) IL-6 (P0.001) did not decrease significantly (P0.05) in active phase and remission period (P0.05), while the content of visfatin in remission period of AASV was still higher than that before treatment (P0.05). The difference of CRP (P0.001) TNF- 伪 (P0.05) and visfatin (P0.001) between the remission stage and the control group was also found. But IL-6 was close to the normal control group (P0.05). (3). The correlation coefficient between AASV and IL-6 was 0.471 (P0. 001), CRP and TNF- 伪 was 0.315) (P0.05 between), CRP and visfatin was 0.364 (P0.01), and between IL-6 and TNF- 伪 was 0.364 (P0. 01). The correlation coefficient between IL-6 and TNF- 伪 was 0.471 (P0. 001) between), CRP and TNF- 伪 (P0. 05). The correlation coefficient between IL-6 and TNF- 伪 was 0.364 (P0. 01). The correlation coefficient between IL-6 and visfatin was 0.577 (P0.001) and the correlation coefficient between TNF- 伪 and visfatin was 0.550 (P0.001). Conclusion the detection of PR3 and MPO is of great value in the diagnosis of vasculitis. However, because of the long duration of concentration in vivo, the level of ANCA and its target antigen can not be used to predict the activity and therapeutic effect of vasculitis. Remission and / or recurrence. The data showed that the concentrations of serum inflammatory cytokines CRP- 6, TNF- 伪 and visfatin were significantly higher in the active period of AASV than in the control group, and there was a positive correlation between the inflammatory factors and visfatin. In the remission phase, the levels of serum visfatin were decreased in different degrees, but the content of TNF- 伪 was not significantly decreased, and the level of serum visfatin in the remission phase was still higher than that in the active phase. These results suggest that there is a dose-dependent relationship between visfatin and TNF- 伪, and this change of visfatin may also indicate the slow repair of visceral adipocytes in AASV, a chronic expendable disease, during the maintenance period of remission. It can prolong the survival time of neutrophils in patients.
【学位授予单位】:天津医科大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R392

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