基质金属蛋白酶-13和胰岛素样生长因子-1在大骨节病关节滑膜中的表达及临床意义

目的 探讨基质金属蛋白酶(MMP-13)和胰岛素样生长因子(IGF)-l在膝关节骨关节炎(OA)和大骨节病(KBD)滑膜病变中的作用机制并比较其异同.方法 提取18例OA患者,13例KBD患者,6名健康对照者的滑膜组织及关节液,采用免疫组织化学方法检测关节滑膜组织中MMP-13和IGF-1的阳性染色区的平均吸光度(A),通过酶联免疫吸附试验(ELISA)法测定关节滑液中MMP-13和IGF-1的蛋白含量.采用单因素方差分析和LSD-t检验进行统计学分析.结果 在本组37份关节滑膜组织及关节滑液标本中:①KBD患者滑膜组织各层MMP-13阳性染色区的4值(692±131,354±10l,415±62)与OA组患者滑膜组织各层平均A(452±57,366±65,652±86)比较差异无统计学意义(P＞0.05),与健康对照组各层A值(541±98,524±202,379±94)比较差异有统计学意义(P＜0.05).②KBD患者滑膜组织各层lGF-1蛋白表达的A值(3ll±174,235±95,412±109)低于OA组(452±57,652±75,544±64)及健康对照组(25l±29,336±54,388±76),且差异有统计学意义(P＜0.05).③KBD患者关节滑液MMP-13含量(2.02±1.12)与OA组(0.93±0.51)比较差异无统计学意义(P＞0.05),但高于健康对照组(2.33±0.29),且差异有统计学意义(P＜0.05).④KBD患者关节滑液IGF-1含量(2.87±1.48)高于OA组(1.27±0.33)和健康对照组(0.93±1.07)且差异均有统计学意义(P＜0.05).结论 ①与OA一样,KBD患者关节的滑膜病变可能作为软骨退变和关节毁损的一个环节而存在;②MMP-13作为OA发病机制中软骨细胞外基质(ECM)主要的分解性因子,可能参与了OA和KBD患者滑膜病理演变过程;③IGF-1作为ECM合成性因子,也参与了OA和KBD患者的滑膜病变过程,但对两种疾病ECM的修复机制可能不同.

Expression and clinical significance of matrix metailoproteinase-13 and insulin-like growth factor-1 in the synovial lesion of Kashin-Beck disease

Objective To discuss the matrix metalloproteinase ( MMP- 13 ) and insulin-like growth factor (IGF)-1 in knee osteoarthritis (OA) and Kashin-Beck disease (KBD) and to explore the mechanism of synovial lesions and their similarities and differences are compared. Methods Synovial fluid of 18 OA patients, 13 KBD patients, 6 normal controls were collected and their synovium were obtained at the same time.The synovium MMP-13 and IGF-1 were examined by immunohistochemistry, while those of the synovial fluid were tested by enzyme-linked immunosorbent assay (ELISA). One way ANOVA and LSD-t test were used for statistical analysis. Results The results of these 37 synovial tissue and synovial fluid samples showed that: ① The average optical density of the positive staining of the KBD synovial tissue (692±131,354±101, 415±62) was not statistically significant from that of the OA group (452±57, 366±65, 652±86)(P＞0.05) and the control group (541±98, 524±202, 379±94, P＜0.05). ②There was significant different between the expression of IGF-1 of synovial tissue in the KBD group (311±174, 235±95, 412±109) and the OA group (452±57, 652±75, 544±64) as well as the control group (251±29, 336±54, 388±76)(P＜0.05).③ Compared with the concentration of MMP-13 in the synovial fluid of the OA group (0.93±0.51), there was no significant difference between the OA and the KBD group (2.02±1.12) (P＞0.05); but, there was significant differences when compared with the control group (2.33 ±0.29, P＜0.05). ④ When compared the the concentration of IGF-1 in the synovial fluid in the KBD group [ (2.87±1.48) and the OA group (1.27±0.33)as well as that of the eontrol group (0.93±1.07)] the difference was significant. Conclusions ① Cartilagedegeneration and joint damage may be a part of the articular synovial lesions in KBD patients, just like that of the OA, and the may exist as a part of the pathogenesis. ② MMP-13 may be involved in the synovial damage,and is the major degenerating factors in cartilage extracellular matrix (ECM) in OA patients and KBD patients. ③ As one of the ECM synthesis factors, IGF-1 may play an important role in the synovial damage of OA and KBD disease, but the repair mechanism may be different between the two diseases.