小劑量糖皮質(zhì)激素對類風濕關(guān)節(jié)炎骨代謝及炎性因子IL-6的作用研究
發(fā)布時間：2019-05-31 18:32
【摘要】：目的:類風濕關(guān)節(jié)炎(rheumatoid arthritis,RA)是一種原因不明的全身性自身免疫性疾病,臨床上大部分患者以慢性或急性侵蝕性關(guān)節(jié)炎為特征表現(xiàn),可導(dǎo)致關(guān)節(jié)強直、畸形甚至功能喪失,嚴重影響患者生活質(zhì)量。近年來糖皮質(zhì)激素(glucocorticoid,GC)在RA治療中占有重要的地位,尤其是小劑量GC在治療RA中的應(yīng)用日益得到廣泛接受。小劑量GC可迅速控制炎癥,緩解關(guān)節(jié)癥狀,同時GC可對骨代謝產(chǎn)生一定的影響。其中在骨代謝指標中具有代表性的是骨形成指標I型原膠原N-端前肽(procollagen I N-terminal peptide,PINP)和骨吸收指標I型膠原C末端肽(C-terminal telopeptide of type I collagen,CTX-1)。本研究通過檢測應(yīng)用小劑量GC的RA患者血清中骨代謝參數(shù)PINP、CTX-1和炎性因子白細胞介素6(interleukin-6,IL-6)水平表達,以及與疾病活動指標和其他臨床指標的相關(guān)關(guān)系,進一步探討長期應(yīng)用小劑量GC對RA患者的利弊,為小劑量GC在RA患者中的應(yīng)用提供理論依據(jù)。方法:選取住院RA患者60例,其中未應(yīng)用GC組(NGC)30例,口服小劑量GC治療3個月以上組(LGC)30例,入選者均應(yīng)用改變病情抗風濕藥(disease modifying antirheumatic drugs,DMARDs),均符合美國風濕病協(xié)會(American College of Rheumatology,ACR)和歐洲抗風濕病聯(lián)盟(European League Against Rheumatism,EULAR)2009年修訂的RA新診斷標準,均除外合并其它類型的免疫性疾病以及嚴重心、腦、肝等器官疾病或功能衰竭者;正常對照組20例,為河北醫(yī)科大學(xué)第三醫(yī)院體檢中心健康體檢者。采用雙抗體夾心酶聯(lián)免疫法(avidin biotin peroxidase complex enzyme-linked immunosorbent assay,ABC-ELISA)檢測所有入組者外周血中PINP、CTX-1、IL-6的水平。同時記錄受試者的性別、年齡、類風濕因子(rheumatoid factor,RF)、紅細胞沉降率(erythrocyte sedimentation rate,ESR)、C-反應(yīng)蛋白(C-reactive protein,CRP)、計算疾病活動性評分(28-joint disease activity scale,DAS28)等臨床指標。分別將RA組與正常組比較,NGC組與LGC組比較,并分別分析PINP、CTX-1、IL-6表達水平變化特點。將PINP、CTX-1、IL-6表達水平與臨床指標之間進行相關(guān)性分析。將PINP、CTX-1、IL-6三者之間進行相關(guān)性分析。所有資料均用SPSS 19.0統(tǒng)計軟件處理。所用計量資料用均數(shù)±標準差表示,符合正態(tài)分布的兩組間比較采用兩樣本均數(shù)比較的t或t’檢驗,相關(guān)性采用直線相關(guān)分析,以P0.05認為差異有統(tǒng)計學(xué)意義。結(jié)果:1一般資料的描述:60例RA患者,女性47例,男性13例,患者年齡22-71歲,平均年齡(50.37±13.09)歲;其中NGC組30例,女性23例,男性7例,患者年齡22-70歲,平均年齡(47.10±13.79)歲;LGC組30例,女性24例,男性6例,患者年齡27-71歲,平均年齡(53.63±11.67)歲。正常對照組20例,其中女性16例,男性4例,患者年齡26-72歲,平均年齡(47.70±12.72)歲。NGC組、LGC組與正常對照組在性別、年齡構(gòu)成方面均無統(tǒng)計學(xué)差異(P0.05)。NGC的RA患者臨床指標CRP(41.98±37.14)mg/L,ESR(68.40±27.50)mm/h,DAS28評分(5.63±0.95),LGC的RA患者臨床指標CRP(34.60±28.04)mg/L,ESR(58.17±24.93)mm/h,DAS28評分(5.31±1.21),NGC組與LGC組在CRP、ESR、DAS28方面差異均無統(tǒng)計學(xué)意義(P0.05)。2血清中PINP、CTX-1、IL-6水平表達2.1 RA組與正常對照組比較:血清PINP、CTX-1、IL-6的水平在RA患者中分別為(19.48±3.58)μg/L、(89.22±16.99)ng/m L、(60.71±11.46)ng/L,在正常對照組中分別為(17.27±3.22)μg/L、(75.35±12.83)ng/m L、(48.81±8.49)ng/L,與正常對照組相比,RA患者血清PINP、CTX-1、IL-6水平升高,差異有統(tǒng)計學(xué)意義(P0.05)。2.2 NGC組與LGC組比較:血清PINP、CTX-1、IL-6的水平在NGC組的RA患者中分別為(20.28±3.56)μg/L、(91.20±17.27)ng/m L、(63.49±11.98)ng/L,在LGC組的RA患者中分別為(18.67±3.47)μg/L、(87.24±16.76)ng/m L、(57.93±10.36)ng/L,與NGC組相比,LGC組血清PINP、CTX-1、IL-6均數(shù)水平相對較低,但差異無統(tǒng)計學(xué)意義(P0.05)。2.3 PINP、CTX-1以及IL-6與臨床指標的相關(guān)性:通過分析得出RA患者PINP與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)均無明顯相關(guān)性;CTX-1與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)亦均無明顯相關(guān)性;IL-6與ESR(r=0.659,P=0.000)、CRP(r=0.427,P=0.001)、DAS28(r=0.359,P=0.005)呈顯著正相關(guān);IL-6與RF(r=-0.096,P=0.466)無明顯相關(guān)性。2.4 PINP、CTX-1及IL-6三個指標的相關(guān)性:通過直線相關(guān)分析可知PINP與CTX-1呈顯著正相關(guān)(r=0.460,P=0.000);PINP與IL-6呈顯著正相關(guān)(r=0.225,P=0.045);CTX-1與IL-6呈顯著正相關(guān)(r=0.388,P=0.000)。結(jié)論:1 RA患者血清中PINP、CTX-1、IL-6水平明顯高于正常對照組,說明RA患者存在骨轉(zhuǎn)換增高。2應(yīng)用小劑量GC組PINP、CTX-1、IL-6與未應(yīng)用組無顯著差異,說明在治療RA中小劑量GC的應(yīng)用沒有明顯導(dǎo)致骨轉(zhuǎn)換增高。3 PINP、CTX-1的血清水平與患者的臨床炎性指標、病情活動度及RF無明顯相關(guān)性,而IL-6與臨床炎性指標、病情活動度呈顯著相關(guān),說明IL-6在RA的炎癥過程中起到一定的作用,IL-6可作為臨床評估RA疾病活動的一個指標。4 PINP、CTX-1及IL-6三個指標之間的呈顯著相關(guān)性,說明IL-6在骨代謝調(diào)節(jié)過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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R593.22
本文編號：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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R593.22
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