类风湿关节炎患者甲襞微循环的变化及可能机制

发布时间：2018-07-02 09:05

本文选题：关节炎 + 类风湿　；参考：《河北医科大学》2015年硕士论文

【摘要】：目的:类风湿关节炎(rheumatoid arthritis,RA)是一种弥漫性结缔组织病,其特点是滑膜炎和血管炎,逐渐侵蚀,造成关节破坏。有多种结缔组织病存在甲襞微循环异常,RA也不例外。本研究旨在通过观察类风湿关节炎患者病程和疾病活动程度不同阶段甲襞微循环的改变,同时检测RA患者血清一氧化氮(nitric oxide,NO)、内皮素-1(endothelin-1,ET-1)及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平,以了解RA患者甲襞微循环的改变及其与内皮因子之间的相关性,探索甲襞微循环改变在RA发病中的作用。方法:1选取确诊RA患者80例。按RA患者病程长短分组:早期组(病程≤2年)、中期组(病程2~5年)和晚期组(病程≥5年)。按RA患者疾病活动程度分组(以DAS28-ESR为标准):高度活动组(DAS285.1)和中低度活动组(DAS28 2.6~5.1)。2对RA患者进行甲襞微循环检查并记录甲襞微循环的形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长。应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清中ET-1和VEGF的表达,采用硝酸还原酶法检测血清中NO的表达,并观察患者有无肺间质病变。比较各组间甲襞微循环、NO、ET-1和VEGF的差异,并对甲襞微循环各项指标与NO、ET-1及VEGF进行相关性分析。3采用SPSS 21.0软件进行数据统计分析。结果:1一般资料1.1高度活动组:58例,其中女性41例,男性17例。平均年龄(48.53±13.26)岁。中低度活动组:22例,其中女性14例,男性8例。平均年龄(46.27±17.44)岁。两组间年龄和性别比较无统计学差异(P0.05)。1.2早期组(病程≤2年):40例,其中女性32例,男性8例。平均年龄(43.88±16.89)岁。中期组(病程2~5年):16例,其中女性9例,男性7例。平均年龄(47.94±10.06)岁。晚期组(病程≥5年):24例,其中女性17例,男性7例。平均年龄(54.92±9.52)岁。早期组和晚期组年龄比较存在统计学差异(P0.05),而早期组和中期组、中期组和晚期组无差异(P均0.05)。三组间性别比较无差异(P0.05)。2甲襞微循环2.1高度活动组:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别为2.08±2.32、0.61±0.76、2.28±1.03、4.62±2.07、(7.16±3.24)um、(7.42±2.29)um、(11.68±3.97)um、(181.00±72.17)um;中低度活动组:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别为1.55±0.55、0.30±0.29、1.49±0.91、3.31±1.22、(6.85±1.52)um、(7.77±2.05)um、(9.85±3.21)um、(183.15±59.29)um。高度活动组在袢周积分和总积分中明显高于中低度活动组(P0.05)。两组在形态积分、流态积分、管袢长、输入枝管径、输出枝管径及袢顶直径无统计学差异(P0.05)。2.2早期组:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别为1.61±0.82、0.22±0.17、1.81±1.17、5.20±8.52、(6.96±2.61)um、(7.81±2.11)um、(11.30±4.35)um、(190.93±74.39)um;中期组:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别为1.68±0.64、0.26±0.16、2.39±1.04、4.33±1.43、(6.45±2.07)um、(7.09±2.30)um、(11.00±3.19)um、(166.00±55.48)um;晚期组:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别为1.86±0.97、0.32±0.16、2.06±1.29、4.24±3.70、(7.88±3.82)um、(7.36±2.53)um、(10.64±3.50)um、(177.21±69.92)um。早期组流态积分明显低于晚期组(P0.05),而早期组与中期组、中期组与晚期组无差别(P0.05)。三组间的形态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长均无差异(P0.05)。3血清NO、ET-1、VEGF表达水平3.1高度活动组:血清NO、ET-1、VEGF分别为(24.86±20.41)umol/L、(119.02±37.68)ng/ml和(54.16±33.28)pg/ml;中低度活动组:血清NO、ET-1、VEGF分别为(24.67±13.21)umol/L、(131.06±35.43)ng/ml、(33.47±9.68)pg/ml。高度活动组血清VEGF明显高于中低度活动组(P0.05),两组间血清NO和血清ET-1无差异(P0.05)。3.2早期组:血清NO、ET-1、VEGF分别为(21.59±11.45)umol/L、(133.48±28.88)ng/ml、(33.47±19.68)pg/ml;中期组:血清NO、ET-1、VEGF分别为(24.46±11.31)umol/L、(120.01±42.26)ng/ml、(61.65±43.27)pg/ml;晚期组:血清NO、ET-1、VEGF分别为(25.48±27.98)umol/L、(101.12±39.03)ng/ml、(53.43±88.45)pg/ml。三组间血清NO、ET-1和VEGF无统计学差异(P0.05)。4甲襞微循环与血清NO、ET-1、VEGF表达水平的相关性分析4.1甲襞微循环与血清NO:流态积分、袢周积分及总积分分别与血清NO呈负相关(相关系数r分别为-0.225,-0.210,-0.256,P均0.05)。然而,形态积分、输入枝管径、输出枝管径、袢顶直径及管袢长与血清NO无相关性(P均0.05)。4.2甲襞微循环与血清ET-1:形态积分及总积分分别与血清ET-1水平呈正相关(相关系数r分别为0.262,0.267,P0.05),输入枝管径、输出枝管径、管袢长分别与血清ET-1呈负相关(相关系数r分别为-0.323,-0.408,-0.261,P0.05)。流态积分、袢周积分及袢顶直径分别与血清ET-1无相关性(P0.05)。4.3甲襞微循环与血清VEGF:形态积分、流态积分、袢周积分、总积分、输入枝管径、输出枝管径、袢顶直径及管袢长分别与血清VEGF水平无相关性(P均0.05)。结论:1高度活动组的甲襞微循环袢周积分和总积分高于中低度活动组,表明微循环异常在RA的发病过程中可能起一定作用。2高度活动组血清VEGF浓度高于中低度活动组,表明VEGF在RA的发病过程中可能起一定作用。1 RA患者的微循环血管损伤与NO和ET-1有关。
[Abstract]:Objective: rheumatoid arthritis (RA) is a diffuse connective tissue disease characterized by synovitis and vasculitis, gradually eroding and causing joint destruction. There are a variety of connective tissue diseases with abnormal nailfold microcirculation and RA. The purpose of this study was to observe the course of disease and the degree of disease activity in patients with rheumatoid arthritis. The changes in the nailfold microcirculation at the same stage were used to detect the levels of nitric oxide (NO), endothelin -1 (endothelin-1, ET-1) and vascular endothelial growth factor (vascular endothelial growth factor, VEGF) in RA patients, in order to understand the changes in the Nailfold Microcirculation and the correlation between the Nailfold Microcirculation and the endothelial factors and explore the nail fold. Methods: the role of microcirculation changes in the pathogenesis of RA. 1 select 80 patients with confirmed RA. According to the duration of RA, early group (course of disease is less than 2 years), medium group (course of disease 2~5) and late group (course of disease > 5 years). According to the degree of disease activity of RA patients (DAS28-ESR as the standard): high activity group (DAS285.1) and middle and low activity group (DAS28 2.6~5.1) .2 was used to examine the Nailfold Microcirculation and to record the form integral of nailfold microcirculation, the integral of the nailfold microcirculation, the integral of the loop, the total integral, the input branch diameter, the output branch diameter, the diameter of the loop top and the length of the loop. The expression of ET-1 and VEGF in serum was detected by enzyme linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA), and the nitrate reductase was used. The expression of NO in the serum was detected and the pulmonary interstitial lesions were observed in the patients. The differences of nailfold microcirculation, NO, ET-1 and VEGF were compared in each group. The correlation analysis of various indexes of Nailfold Microcirculation with NO, ET-1 and VEGF was used to analyze.3 using SPSS 21 software. Results: 1 general data 1.1 highly active group: 58 cases, of which 4 women were 4. 1 cases, 17 cases of average age (48.53 + 13.26). Middle and low activity group: 22 cases, 14 women and 8 men. The average age was (46.27 + 17.44) years. The age and sex of the two groups were not statistically different (P0.05) in the early.1.2 group (the course of the disease was less than 2 years): 40 cases, among them, the average age (2~5). 16 cases, including 9 women and 7 men. The average age (47.94 + 10.06) years. The late group (course of disease > 5 years): 24 cases, including 17 women and 7 men. The average age is (54.92 + 9.52) years. There is a statistical difference between the early and late group (P0.05), but there is no difference between the early group and the middle group, the middle group and the late group (P 0.05). Three groups. No difference (P0.05).2 nailfold microcirculation 2.1 high activity group: shape integral, flow integral, loop integral, total integral, input branch pipe diameter, output branch diameter, loop top diameter and loop length are 2.08 + 2.32,0.61 + 0.76,2.28 + 1.03,4.62 + 2.07, (7.16 + 3.24) um, (7.42 + 2.29) um, (11.68 + 3.97) um, (181 + 72.17) um; middle and low activity Group: morphological integral, flow integral, loop integral, total integral, input branch pipe diameter, output branch pipe diameter, loop top diameter and loop length were 1.55 + 0.55,0.30 + 0.29,1.49 + 0.91,3.31 + 1.22, (6.85 + 1.52) um, (7.77 + 2.05) um, (9.85 + 3.21) um and (183.15 + 59.29) um. high activity group were obviously higher than middle and low activity in loop integral and total integral. Group (P0.05). In the two group, the form integral, the manifold integral, the length of the pipe loop, the input branch pipe diameter, the output branch pipe diameter and the loop top diameter have no statistical difference (P0.05) early.2.2 group: the shape integral, the flow integral, the loop integral, the total integral, the input branch pipe diameter, the output branch pipe diameter, the loop top diameter and the loop length are respectively 1.61 + 0.82,0.22 + 0.17,1.81 + 1.17,5.20 + 8.52, respectively. (6.96 + 2.61) um, (7.81 + 2.11) um, (11.30 + 4.35) um, (190.93 + 74.39) um, medium group: form integral, flow integral, loop integral, total integral, input branch diameter, output branch diameter, loop top diameter and loop length are 1.68 + 0.64,0.26 + 0.16,2.39 + 1.43, (6.45 + 2.07) um, (7.09 + 74.39) um, um; um; night um; um; late um, um; um; late um, um; night um; um; late um, um; night um; um; night um; um; late um. Night um; um; night um; um; night um; um; night um; um; um; late um, um; um; night um; um; night um; um; night um; um; um; late um, um; um; night um; um; um; late um. Period group: form integral, flow integral, loop integral, total integral, input branch pipe diameter, output branch pipe diameter, loop top diameter and loop length are 1.86 + 0.97,0.32 + 0.16,2.06 + 1.29,4.24 + 3.70, (7.88 + 3.82) um, (7.36 + 2.53) um, (10.64 + 3.50) um, (177.21 + 69.92) um. early group flow integral is obviously lower than that in late group (P0.05), and early group and middle There was no difference between the mid-term group and the late group (P0.05). The morphological integral of the three groups, loop integral, total integral, the input branch diameter, the output branch diameter, the diameter of the loop top and the length of the loop were not different (P0.05).3 serum NO, ET-1, VEGF expression level in the high activity group: the serum NO, ET-1, VEGF were (24.86 + 20.41) umol/L, (119.02 + 37.68) ng/ml and (54.16 + 3). 3.28) pg/ml; middle and low activity group: serum NO, ET-1, VEGF were (24.67 + 13.21) umol/L, (131.06 + 35.43) ng/ml, and (33.47 + 9.68) pg/ml. high activity group was significantly higher than middle and low activity group (P0.05). The serum NO and serum ET-1 were no difference between two groups (P0.05) early group: (21.59 + 11.45) respectively, (133.48 + 2) 8.88) ng/ml, (33.47 + 19.68) pg/ml, medium group: serum NO, ET-1, VEGF, respectively (24.46 + 11.31) umol/L, (120.01 + 42.26) ng/ml, (61.65 + 43.27) pg/ml, and late group: serum NO, ET-1, VEGF respectively (25.48 + 27.98) umol/L, (101.12 + 39.03) Correlation analysis of the expression level of NO, ET-1, VEGF in the ring and serum, 4.1 nailfold microcirculation and serum NO: flow integration, loop integral and total integral were negatively correlated with serum NO (the correlation coefficient r was -0.225, -0.210, -0.256, P 0.05 respectively). However, the morphological integral, the input branch diameter, the output branch pipe diameter, the loop top diameter and the loop length were not different from the serum NO. The P 0.05.4.2 nailfold microcirculation and the integral integral and total integral of serum ET-1: were positively correlated with the level of serum ET-1 respectively (the correlation coefficient r was 0.262,0.267, P0.05), the input branch diameter, the output branch diameter, and the length of the loop of the tube were negatively correlated with the serum ET-1 (the correlation coefficient r is -0.323, -0.408, -0.261, etc.). No correlation (P0.05).4.3 nailfold microcirculation and serum VEGF: form integration with serum ET-1. Flow integral, loop integral, total integral, input branch diameter, output branch diameter, loop top diameter and loop length were not related to serum VEGF level respectively (P 0.05). Conclusion: the weekly integral of Nailfold Microcirculation loop in the 1 high activity group and The total integral is higher than the middle and low activity group, which indicates that the microcirculation abnormal in the pathogenesis of RA may play a role in.2 high activity group, the serum VEGF concentration is higher than the middle and low activity group, which indicates that VEGF may play a role in the microcirculatory vascular damage of.1 RA patients during the pathogenesis of RA, which is related to NO and ET-1.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.22

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