小剂量糖皮质激素对类风湿关节炎骨代谢及炎性因子IL-6的作用研究
发布时间：2019-05-31 18:32
【摘要】：目的:类风湿关节炎(rheumatoid arthritis,RA)是一种原因不明的全身性自身免疫性疾病,临床上大部分患者以慢性或急性侵蚀性关节炎为特征表现,可导致关节强直、畸形甚至功能丧失,严重影响患者生活质量。近年来糖皮质激素(glucocorticoid,GC)在RA治疗中占有重要的地位,尤其是小剂量GC在治疗RA中的应用日益得到广泛接受。小剂量GC可迅速控制炎症,缓解关节症状,同时GC可对骨代谢产生一定的影响。其中在骨代谢指标中具有代表性的是骨形成指标I型原胶原N-端前肽(procollagen I N-terminal peptide,PINP)和骨吸收指标I型胶原C末端肽(C-terminal telopeptide of type I collagen,CTX-1)。本研究通过检测应用小剂量GC的RA患者血清中骨代谢参数PINP、CTX-1和炎性因子白细胞介素6(interleukin-6,IL-6)水平表达,以及与疾病活动指标和其他临床指标的相关关系,进一步探讨长期应用小剂量GC对RA患者的利弊,为小剂量GC在RA患者中的应用提供理论依据。方法:选取住院RA患者60例,其中未应用GC组(NGC)30例,口服小剂量GC治疗3个月以上组(LGC)30例,入选者均应用改变病情抗风湿药(disease modifying antirheumatic drugs,DMARDs),均符合美国风湿病协会(American College of Rheumatology,ACR)和欧洲抗风湿病联盟(European League Against Rheumatism,EULAR)2009年修订的RA新诊断标准,均除外合并其它类型的免疫性疾病以及严重心、脑、肝等器官疾病或功能衰竭者;正常对照组20例,为河北医科大学第三医院体检中心健康体检者。采用双抗体夹心酶联免疫法(avidin biotin peroxidase complex enzyme-linked immunosorbent assay,ABC-ELISA)检测所有入组者外周血中PINP、CTX-1、IL-6的水平。同时记录受试者的性别、年龄、类风湿因子(rheumatoid factor,RF)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、C-反应蛋白(C-reactive protein,CRP)、计算疾病活动性评分(28-joint disease activity scale,DAS28)等临床指标。分别将RA组与正常组比较,NGC组与LGC组比较,并分别分析PINP、CTX-1、IL-6表达水平变化特点。将PINP、CTX-1、IL-6表达水平与临床指标之间进行相关性分析。将PINP、CTX-1、IL-6三者之间进行相关性分析。所有资料均用SPSS 19.0统计软件处理。所用计量资料用均数±标准差表示,符合正态分布的两组间比较采用两样本均数比较的t或t’检验,相关性采用直线相关分析,以P0.05认为差异有统计学意义。结果:1一般资料的描述:60例RA患者,女性47例,男性13例,患者年龄22-71岁,平均年龄(50.37±13.09)岁;其中NGC组30例,女性23例,男性7例,患者年龄22-70岁,平均年龄(47.10±13.79)岁;LGC组30例,女性24例,男性6例,患者年龄27-71岁,平均年龄(53.63±11.67)岁。正常对照组20例,其中女性16例,男性4例,患者年龄26-72岁,平均年龄(47.70±12.72)岁。NGC组、LGC组与正常对照组在性别、年龄构成方面均无统计学差异(P0.05)。NGC的RA患者临床指标CRP(41.98±37.14)mg/L,ESR(68.40±27.50)mm/h,DAS28评分(5.63±0.95),LGC的RA患者临床指标CRP(34.60±28.04)mg/L,ESR(58.17±24.93)mm/h,DAS28评分(5.31±1.21),NGC组与LGC组在CRP、ESR、DAS28方面差异均无统计学意义(P0.05)。2血清中PINP、CTX-1、IL-6水平表达2.1 RA组与正常对照组比较:血清PINP、CTX-1、IL-6的水平在RA患者中分别为(19.48±3.58)μg/L、(89.22±16.99)ng/m L、(60.71±11.46)ng/L,在正常对照组中分别为(17.27±3.22)μg/L、(75.35±12.83)ng/m L、(48.81±8.49)ng/L,与正常对照组相比,RA患者血清PINP、CTX-1、IL-6水平升高,差异有统计学意义(P0.05)。2.2 NGC组与LGC组比较:血清PINP、CTX-1、IL-6的水平在NGC组的RA患者中分别为(20.28±3.56)μg/L、(91.20±17.27)ng/m L、(63.49±11.98)ng/L,在LGC组的RA患者中分别为(18.67±3.47)μg/L、(87.24±16.76)ng/m L、(57.93±10.36)ng/L,与NGC组相比,LGC组血清PINP、CTX-1、IL-6均数水平相对较低,但差异无统计学意义(P0.05)。2.3 PINP、CTX-1以及IL-6与临床指标的相关性:通过分析得出RA患者PINP与ESR(r=-0.059,P=0.654)、CRP(r=0.047,P=0.721)、DAS28(r=-0.141,P=0.282)、RF(r=-0.057,P=0.665)均无明显相关性;CTX-1与ESR(r=0.048,P=0.714)、CRP(r=0.053,P=0.688)、DAS28(r=-0.031,P=0.816)、RF(r=-0.083,P=0.528)亦均无明显相关性;IL-6与ESR(r=0.659,P=0.000)、CRP(r=0.427,P=0.001)、DAS28(r=0.359,P=0.005)呈显著正相关;IL-6与RF(r=-0.096,P=0.466)无明显相关性。2.4 PINP、CTX-1及IL-6三个指标的相关性:通过直线相关分析可知PINP与CTX-1呈显著正相关(r=0.460,P=0.000);PINP与IL-6呈显著正相关(r=0.225,P=0.045);CTX-1与IL-6呈显著正相关(r=0.388,P=0.000)。结论:1 RA患者血清中PINP、CTX-1、IL-6水平明显高于正常对照组,说明RA患者存在骨转换增高。2应用小剂量GC组PINP、CTX-1、IL-6与未应用组无显著差异,说明在治疗RA中小剂量GC的应用没有明显导致骨转换增高。3 PINP、CTX-1的血清水平与患者的临床炎性指标、病情活动度及RF无明显相关性,而IL-6与临床炎性指标、病情活动度呈显著相关,说明IL-6在RA的炎症过程中起到一定的作用,IL-6可作为临床评估RA疾病活动的一个指标。4 PINP、CTX-1及IL-6三个指标之间的呈显著相关性,说明IL-6在骨代谢调节过程中起到一定的作用。
[Abstract]:Objective: Rheumatoid arthritis (RA) is an unknown systemic autoimmune disease, and most of the patients are characterized by chronic or acute aggressive arthritis. In recent years, Glucocorticoid (GC) plays an important role in the treatment of RA, especially the application of low-dose GC in the treatment of RA has been widely accepted. The low-dose GC can rapidly control the inflammation and relieve the joint symptoms, and the GC can have a certain effect on the bone metabolism. Among them, the bone-forming index I-type procollagen N-terminal propeptide (PINP) and bone resorption index type I collagen C-terminal peptide (CTX-1) are representative in the bone metabolism index. This study further discussed the advantages and disadvantages of long-term application of low-dose GC to RA patients by detecting the levels of PINP, CTX-1 and interleukin-6 (IL-6) levels in the serum of RA patients using low-dose GC, as well as the related relationship with the disease activity index and other clinical indicators. To provide a theoretical basis for the application of low-dose GC in patients with RA. Methods:60 patients with RA were selected, in which 30 patients were not treated with GC (NGC), and 30 cases (LGC) were treated with low-dose GC. All the patients were treated with the disease-resistant antirheumatic drugs (DMARDs). All of them were in accordance with American College of Rheology. The new diagnostic criteria for RA, as amended in 2009 by the European League of Rheumatology (EURAR), are excluded from the combination of other types of immune diseases and other organ diseases or functional failure of the heart, the brain, the liver and the like; in the normal control group,20 cases, The medical examination center for the third hospital of the medical university of hebei medical university. The levels of PINP, CTX-1 and IL-6 in the peripheral blood of all the patients were detected by using a double-antibody sandwich enzyme-linked immunosorbent assay (ABC-ELISA). The subjects' sex, age, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity scale (DAS28) were recorded. The changes of the expression of PINP, CTX-1 and IL-6 were compared with those of the normal group, the NGC group and the LGC group, respectively. The expression level of PINP, CTX-1, IL-6 and the clinical index were analyzed. The correlation between PINP, CTX-1 and IL-6 was analyzed. All data were processed with SPSS 19.0. The mean square standard deviation of the used measurement data indicated that the two groups that met the normal distribution adopt the t or t 'test of the same mean number comparison, the correlation is the linear correlation analysis, and the difference is considered to be of statistical significance. Results:1 General data description:60 patients with RA, 47 cases of female,13 male,22-71 years old, mean age (50.37, 13.09) years old, including 30 cases of NGC group,23 cases of female,7 cases of male,22-70 years old, mean age (47.10-13.79) years old,30 cases of LGC group,24 cases of female,6 cases of male, and 27-71 years of age. The mean age (53.63-11.67) years. The average age (53.63-11.67) years. In the normal control group, there were 16 males and 4 females, and the age of the patients was 26-72 years. The mean age (47.70-12.72) years. The NGC group, the LGC group and the normal control group were gender, The clinical index of CRP (41.98% 37.14) mg/ L, ESR (68.40-27.50) mm/ h, DAS28 score (5.63-0.95), CRP (34.60-28.04) mg/ L, ESR (58.17-24.93) mm/ h, DAS28 score (5.31-1.21), NGC group and LGC group in CRP and ESR in patients with RA of NGC were no significant difference (P0.05). The levels of PINP, CTX-1 and IL-6 in serum were compared with those of normal control group. The levels of serum PINP, CTX-1 and IL-6 were (19.48-3.58). m/ L, (89.22-16.99) ng/ mL, (60.71-11.46) ng/ L, respectively. The levels of serum PINP, CTX-1 and IL-6 in patients with RA were significantly higher in the control group (17.27-3.22) and (75.35-12.83) ng/ L, (48.81-8.49) ng/ L, respectively. The levels of IL-6 were (20.28, 3.56). m/ L, (91.20, 17.27) ng/ m L, (63.49, 11.98) ng/ L in the NGC group, respectively (18.67 and 3.47). m u.g/ L, (87.24 to 16.76) ng/ m L, (57.93 to 10.36) ng/ L in the patients with RA in the LGC group, and in the LGC group, the serum PINP, CTX-1, The level of IL-6 was relatively low, but the difference was not significant (P0.05). 2.3 The correlation of PINP, CTX-1, and IL-6 with the clinical index: PINP and ESR (r =-0.059, P = 0.654), CRP (r = 0.047, P = 0.721), DAS28 (r =-0.141, P = 0.282), RF (r =-0.057, P = 0.665) of RA patients were not significantly correlated; CTX-1 and ESR (r = 0.048, P = 0.714), CRP (r = 0.053, P = 0.688), DAS28 (r =-0.031, There was no significant correlation between IL-6 and ESR (r = 0.659, P = 0.000), CRP (r = 0.427, P = 0.001), DAS28 (r = 0.359, P = 0.005), and there was no significant correlation between IL-6 and RF (r =-0.096, P = 0.466). There was a significant positive correlation between PINP and IL-6 (r = 0.225, P = 0.045), and CTX-1 was positively correlated with IL-6 (r = 0.388, P = 0.000). Conclusion: The level of PINP, CTX-1 and IL-6 in serum of patients with RA is significantly higher than that of normal control group. There was no significant difference between IL-6 and the non-applied group. The application of low-dose GC in the treatment of RA did not significantly lead to increased bone turnover. The serum levels of PINP and CTX-1 were not significantly correlated with the clinical inflammatory index, disease activity and RF of the patient, while IL-6 and the clinical inflammatory index, The activity of IL-6 plays a role in the inflammatory process of RA, and IL-6 can be used as an indicator of the clinical evaluation of RA disease activity. The results show that IL-6 plays a role in the regulation of bone metabolism.
【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
本文编号：2489931
[Abstract]:Objective: Rheumatoid arthritis (RA) is an unknown systemic autoimmune disease, and most of the patients are characterized by chronic or acute aggressive arthritis. In recent years, Glucocorticoid (GC) plays an important role in the treatment of RA, especially the application of low-dose GC in the treatment of RA has been widely accepted. The low-dose GC can rapidly control the inflammation and relieve the joint symptoms, and the GC can have a certain effect on the bone metabolism. Among them, the bone-forming index I-type procollagen N-terminal propeptide (PINP) and bone resorption index type I collagen C-terminal peptide (CTX-1) are representative in the bone metabolism index. This study further discussed the advantages and disadvantages of long-term application of low-dose GC to RA patients by detecting the levels of PINP, CTX-1 and interleukin-6 (IL-6) levels in the serum of RA patients using low-dose GC, as well as the related relationship with the disease activity index and other clinical indicators. To provide a theoretical basis for the application of low-dose GC in patients with RA. Methods:60 patients with RA were selected, in which 30 patients were not treated with GC (NGC), and 30 cases (LGC) were treated with low-dose GC. All the patients were treated with the disease-resistant antirheumatic drugs (DMARDs). All of them were in accordance with American College of Rheology. The new diagnostic criteria for RA, as amended in 2009 by the European League of Rheumatology (EURAR), are excluded from the combination of other types of immune diseases and other organ diseases or functional failure of the heart, the brain, the liver and the like; in the normal control group,20 cases, The medical examination center for the third hospital of the medical university of hebei medical university. The levels of PINP, CTX-1 and IL-6 in the peripheral blood of all the patients were detected by using a double-antibody sandwich enzyme-linked immunosorbent assay (ABC-ELISA). The subjects' sex, age, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity scale (DAS28) were recorded. The changes of the expression of PINP, CTX-1 and IL-6 were compared with those of the normal group, the NGC group and the LGC group, respectively. The expression level of PINP, CTX-1, IL-6 and the clinical index were analyzed. The correlation between PINP, CTX-1 and IL-6 was analyzed. All data were processed with SPSS 19.0. The mean square standard deviation of the used measurement data indicated that the two groups that met the normal distribution adopt the t or t 'test of the same mean number comparison, the correlation is the linear correlation analysis, and the difference is considered to be of statistical significance. Results:1 General data description:60 patients with RA, 47 cases of female,13 male,22-71 years old, mean age (50.37, 13.09) years old, including 30 cases of NGC group,23 cases of female,7 cases of male,22-70 years old, mean age (47.10-13.79) years old,30 cases of LGC group,24 cases of female,6 cases of male, and 27-71 years of age. The mean age (53.63-11.67) years. The average age (53.63-11.67) years. In the normal control group, there were 16 males and 4 females, and the age of the patients was 26-72 years. The mean age (47.70-12.72) years. The NGC group, the LGC group and the normal control group were gender, The clinical index of CRP (41.98% 37.14) mg/ L, ESR (68.40-27.50) mm/ h, DAS28 score (5.63-0.95), CRP (34.60-28.04) mg/ L, ESR (58.17-24.93) mm/ h, DAS28 score (5.31-1.21), NGC group and LGC group in CRP and ESR in patients with RA of NGC were no significant difference (P0.05). The levels of PINP, CTX-1 and IL-6 in serum were compared with those of normal control group. The levels of serum PINP, CTX-1 and IL-6 were (19.48-3.58). m/ L, (89.22-16.99) ng/ mL, (60.71-11.46) ng/ L, respectively. The levels of serum PINP, CTX-1 and IL-6 in patients with RA were significantly higher in the control group (17.27-3.22) and (75.35-12.83) ng/ L, (48.81-8.49) ng/ L, respectively. The levels of IL-6 were (20.28, 3.56). m/ L, (91.20, 17.27) ng/ m L, (63.49, 11.98) ng/ L in the NGC group, respectively (18.67 and 3.47). m u.g/ L, (87.24 to 16.76) ng/ m L, (57.93 to 10.36) ng/ L in the patients with RA in the LGC group, and in the LGC group, the serum PINP, CTX-1, The level of IL-6 was relatively low, but the difference was not significant (P0.05). 2.3 The correlation of PINP, CTX-1, and IL-6 with the clinical index: PINP and ESR (r =-0.059, P = 0.654), CRP (r = 0.047, P = 0.721), DAS28 (r =-0.141, P = 0.282), RF (r =-0.057, P = 0.665) of RA patients were not significantly correlated; CTX-1 and ESR (r = 0.048, P = 0.714), CRP (r = 0.053, P = 0.688), DAS28 (r =-0.031, There was no significant correlation between IL-6 and ESR (r = 0.659, P = 0.000), CRP (r = 0.427, P = 0.001), DAS28 (r = 0.359, P = 0.005), and there was no significant correlation between IL-6 and RF (r =-0.096, P = 0.466). There was a significant positive correlation between PINP and IL-6 (r = 0.225, P = 0.045), and CTX-1 was positively correlated with IL-6 (r = 0.388, P = 0.000). Conclusion: The level of PINP, CTX-1 and IL-6 in serum of patients with RA is significantly higher than that of normal control group. There was no significant difference between IL-6 and the non-applied group. The application of low-dose GC in the treatment of RA did not significantly lead to increased bone turnover. The serum levels of PINP and CTX-1 were not significantly correlated with the clinical inflammatory index, disease activity and RF of the patient, while IL-6 and the clinical inflammatory index, The activity of IL-6 plays a role in the inflammatory process of RA, and IL-6 can be used as an indicator of the clinical evaluation of RA disease activity. The results show that IL-6 plays a role in the regulation of bone metabolism.
【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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