膝骨关节炎患者软骨容积与关节结构及脂肪细胞因子相关性临床研究

发布时间：2018-04-28 03:19

本文选题：膝骨关节炎 + 关节　；参考：《安徽医科大学》2015年硕士论文

【摘要】：背景骨关节炎(Osteoarthritis,OA)是全球最常见的慢性关节疾病,是中老年人残疾的主要原因。目前,通过放射学检查即X线,已成为临床上诊断OA的金标准,通过X线不能观察到OA早期关节结构改变,这对OA的早期诊断及治疗带来一定程度的困难。磁共振成像(Magnetic Resonance Imaging,MRI)可发现早期、细微的结构改变,因此,MRI越来越多应用到关节疾病的早期诊断及治疗中。近年来,国外有研究证明关节软骨容积(Cartilage Volume,CV)与OA放射学改变包括骨赘(Osteophyte,OP)和关节间隙狭窄(Joint Space Narrowing,JSN)及其它关节结构改变相关,此类研究在我国鲜有报道。肥胖所致关节过度承重是导致膝OA关节结构改变的机制之一,近年来研究表明,脂肪组织可分泌多种脂肪细胞因子,如瘦素(Leptin,LPT)、脂联素(Adiponectin,ADP)、抵抗素(Resistin,RST)等,参与膝OA的发生发展,但膝OA患者关节结构的改变与脂肪细胞因子的作用及临床意义国内尚未见系统性报道。目的分析CV与放射学改变、软骨缺损(Cartilage Defects,CD)、骨髓病变(Bone Marrow Lesions,BMLs)等结构改变及与血清脂肪细胞因子、实验室指标的相关性,以提高对OA的认识,探索可能的早期诊断指标和潜在的治疗靶点。方法收集2012年1月至2013年11月就诊于安徽医科大学第一附属医院风湿科门诊的症状性膝OA患者205例。根据X线,使用凯尔格伦-劳伦斯(Kellgren-Lawrence,KL)对患者膝关节放射学改变严重程度进行评级及使用OA研究协会(Osteoarthritis Research Society International,OARSI)分级标准评估OP、JSN的分级。使用Osiri X软件在MRI测量CV,并评估CD、BMLs的分级。记录患者的临床及实验室指标,根据西安大略和麦克玛斯特大学OA指数评分表(TheWestern Ontario and Mc Master University Osteoarthritis Index,WOMAC)对患者膝关节疼痛、僵硬、关节功能进行评分。用酶联免疫吸附法(Enzyme-linked Immunosorbent Assay,ELISA)检测患者血清LPT、ADP、RST水平。结果1.膝关节CV与临床及实验室指标的相关性:总CV(髌骨、内侧胫骨、外侧胫骨CV之和)仅与WHR有明显正相关(r=0.172,P=0.033);男、女之间CV(髌骨、内侧胫骨、外侧胫骨)有明显的差异性,P值均0.05;有放射学改变与无放射学改变两组间的年龄、病程、总CV、髌骨CV有明显差异性(P值分别为0.003、0.003、0.026、0.028);2.膝关节CV与放射学改变的相关性:髌骨CV在外侧股、胫骨OP组间有明显差异性,内侧胫骨CV在内侧股胫骨JSN组间有明显差异性,内侧及外侧胫骨CV在外侧股胫骨JSN组间有明显差异性(P值均0.05);以CV为因变量(髌骨、内侧胫骨、外侧胫骨),以放射学改变如内侧股胫骨OP、内侧JSN、外侧JSN分别为自变量,进行回归分析,调节混杂因素前后,显示髌骨CV在外侧股胫骨OP负相关(β:-0.103,95%CI:-0.165,-0.040),内侧JSN与内侧胫骨CV负相关(β:-0.090,95%CI:-0.171,-0.009),外侧JSN与外侧胫骨CV负相关(β:-0.125,95%CI:-0.219,-0.030),P值均0.05;3.膝关节CV与关节CD的相关性:分别对CV在不同部位(髌骨、内侧股骨、外侧股骨、内侧胫骨、外侧胫骨)的CD组间的差异性进行比较,结果发现,除了在外侧股骨CD组间未发现CV有明显的差异性,余均能在相应部位的CD组间的CV发现明显差异性(P值均0.05);以关节CV为因变量(髌骨、内侧胫骨、外侧胫骨),以各部位的CD分别为自变量,进行回归分析,调节混杂因素前后,显示特定部位的关节CV与CD负相关,如调节混杂因素后,内侧胫骨CV与内侧胫骨CD负相关(β:-0.114,95%CI:-0.163~-0.064);4.膝关节CV与BMLs的相关性:内侧胫骨CV在相应部位的BMLs分组间有显著性差异;以CV为因变量(内侧胫骨、外侧胫骨),以外侧股骨、外侧胫骨、内侧股骨、外侧股骨BMLs分别为自变量,进行回归分析,调节混杂因素前后,发现内侧胫骨CV与内侧胫骨BMLs负相关(β:-0.042,95%CI:-0.119,-0.024);5.膝关节CV与脂肪细胞因子的相关性:放射学改变和无放射学改变的患者的血清的LPT、ADP、RST分别作为因变量,以各部位CV分别作为自变量,进行单因素分析,结果提示,在有放射学改变的患者中LPT与髌骨、内侧胫骨CV呈明显正相关性,在调节年龄、性别、BMI及病程后,此相关性仍存在(β:10.172,95%CI:1.30 to 17.55;β:6.213,95%CI:2.11 to 10.10);6.脂肪细胞因子与OA放射学改变严重程度的相关性:分别以LPT、ADP、RST作为因变量,以KL分级作为自变量,进行线性回归分析,调整混杂因素前后,ADP与KL分级存在负相关性(OR:0.988,95%CI:0.979 to 0.998),LPT、RST与KL分级均无明显相关性;结论1.膝OA患者中,关节CV与其他关节结构改变明显相关,它可能作为一个较好的临床指标来预测关节结构的改变;2.在脂肪细胞因子中,LPT及ADP可能对OA起保护作用;
[Abstract]:Osteoarthritis (OA) is the most common chronic joint disease in the world. It is the main cause of disability in the middle and old people. At present, by radiological examination, X-ray has become the gold standard for clinical diagnosis of OA. The structural changes of the joint in early OA can not be observed by X-ray. This has brought about a certain degree of difficulties in the early diagnosis and treatment of OA. It is difficult. Magnetic Resonance Imaging (MRI) can detect early and subtle structural changes. Therefore, MRI is increasingly used in the early diagnosis and treatment of joint disease. In recent years, foreign studies have shown that cartilage volume (Cartilage Volume, CV) and OA radiological changes include osteophyte (Osteophyte, OP) and joint space stenosis (Cartilage, OP). Joint Space Narrowing, JSN) and other joint structural changes are related. This kind of study is rarely reported in China. Obesity - induced joint overload is one of the mechanisms that lead to the structural changes of the knee joint. In recent years, studies have shown that adipose tissue can secrete a variety of adipocytokines, such as Leptin (LPT), adiponectin (Adiponectin, ADP), resistin (Joint). Resistin, RST), etc., participate in the development of knee OA, but there is no systematic report on the changes of joint structure and the role and clinical significance of Adipocyte Factor in knee OA patients. Objective to analyze the structural changes of CV and radiological changes, cartilage defect (Cartilage Defects, CD), bone marrow lesions (Bone Marrow Lesions, BMLs) and so on. The correlation of cell factors and laboratory indicators to improve the understanding of OA, explore possible early diagnostic indicators and potential therapeutic targets. Methods 205 patients with symptomatic knee OA from January 2012 to November 2013 in the Department of rheumatism, the First Affiliated Hospital of Medical University Of Anhui were collected, and Kell Glen Laurence (Kellgren-La) was used according to X ray. Wrence, KL) rating the severity of the knee joint radiology and using the OA Research Association (Osteoarthritis Research Society International, OARSI) grading standard to evaluate the classification of OP, JSN. The Mike mast University OA index score (TheWestern Ontario and Mc Master University Osteoarthritis Index, WOMAC) was used to evaluate the pain, stiffness and joint function of the knee joint. Correlation of laboratory indicators: the total CV (the patella, medial tibia, and the CV of the lateral tibia) was only positively correlated with WHR (r=0.172, P=0.033), and there were significant differences in CV (patella, medial tibia, lateral tibia) between men and women, and the P value was 0.05; there was a significant difference between the age of the two groups, the course of the disease, the total CV, and the patellar CV between the radiological changes and the radiological changes. The sex (P value was 0.003,0.003,0.026,0.028); 2. knee joint CV and radiological changes: the patellar CV in the lateral femoral, the tibial OP group was significantly different, the medial tibial CV in the medial tibial JSN group was significantly different, the medial and lateral tibial CV in the lateral tibial JSN group was significantly different (P value was 0.05); CV as the dependent variable. (patella, medial tibia, lateral tibia), with radiological changes such as the medial tibia OP, medial JSN, and lateral JSN as independent variables, regression analysis, before and after the adjustment of the confounding factors, showing the OP negative correlation of the patellar CV in the lateral tibia (beta: -0.103,95%CI:-0.165, -0.040), and the negative correlation between the medial JSN and the medial tibia (beta: -0.090,95%CI:-0.171, -0.009). The negative correlation between lateral JSN and lateral tibia (beta: -0.125,95%CI:-0.219, -0.030), P value of 0.05, and the correlation between CV and joint CD in 3. knee joints: the differences in the CD groups of CV at different parts (patella, medial femur, lateral femur, medial tibia and lateral tibia) were compared. The results showed that CV was not found between the lateral femur CD groups. A significant difference was found in the CV of the corresponding CD groups (P value 0.05). The joint CV was used as the dependent variable (patella, medial tibia, the lateral tibia), and the CD of each part was the independent variable. The regression analysis showed that the joint CV in the specific site was negatively correlated with CD, such as after adjusting the confounding factors, The negative correlation between the medial tibial CV and the medial tibial CD (beta: -0.114,95%CI:-0.163~-0.064), and the correlation between CV and BMLs in the 4. knee joints: the CV in the medial tibia was significantly different between the BMLs groups in the corresponding parts; the independent variable (the medial tibia, the lateral tibia), the lateral femur, the lateral tibia, the medial femur, and the lateral femur BMLs were the independent variables, respectively. The negative correlation between the medial tibial CV and the BMLs of the medial tibia (beta: -0.042,95%CI:-0.119, -0.024) was found before and after the adjustment of the confounding factors. 5. the correlation between CV and adipocytokines in the knee joint: the serum LPT, ADP, RST of the patients with radiological and radiological changes were used as the dependent variables, respectively, as independent variables. Single factor analysis showed that LPT had a significant positive correlation with the patellar and medial tibial CV in patients with radiological changes. This correlation still existed after regulating age, sex, BMI, and the course of disease (beta: 10.172,95%CI:1.30 to 17.55; beta: 6.213,95%CI:2.11 to 10.10); 6. the correlation between adipocytokines and OA radiological changes: LPT, ADP and RST were used as dependent variables, and KL classification was used as independent variable and linear regression analysis was carried out. Before and after the adjustment of mixed factors, there was negative correlation between ADP and KL classification (OR:0.988,95%CI:0.979 to 0.998), LPT, RST and KL classification. As a good clinical indicator to predict changes in joint structure; 2. in LPT, ADP and OA may play a protective role in adipocytokines.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R684.3

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