CAJ | 학술논문

背景：基质金属蛋白酶组织抑制剂1是与基质金属蛋白酶13相对应的拮抗剂，两者间表达水平和功能活性的平衡对细胞外基质的代谢状态起着重要作用，但在 DH 豚鼠骨关节炎发生发展过程中，两者表达水平，尤其两者表达水平比值的变化尚不明确。 　　目的：探讨不同月龄DH豚鼠关节软骨中基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1表达比值的变化及其与DH豚鼠增龄性原发骨性关节炎发病过程中软骨退变程度的关系。 　　方法：选取2，4，8，12月龄雌性DH各6只，取膝关节观察关节软骨的大体形态后常规脱钙、包埋、制作石蜡切片，用于VG染色行组织学观察，采用Mankin评分系统定量分析关节软骨退变情况，采用免疫组织化学方法检测膝关节软骨中基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1表达情况，应用 Image pro-Plus 6.0软件对免疫组织化学阳性蛋白表达情况进行积分吸光度计算。线性回归分析判断Mankin评分与基质金属蛋白酶13/基质金属蛋白酶组织抑制剂1比值的相关性。 　　结果与结论：DH 豚鼠2月龄膝关节软骨无关节炎表现，4月龄出现轻度软骨退变，并随月龄增加进行性加重，Mankin评分随月龄增加逐渐增高，各组之间的差异均有显著性意义(P <0.05)。基质金属蛋白酶13、基质金属蛋白酶组织抑制剂1的表达均随月龄进行性增加，两者比值与Mankin评分呈正相关性(P <0.05)。结果提示DH豚鼠4月龄出现膝关节软骨退行性变化，随月龄增加而进行性加重，其病理改变与基质金属蛋白酶13/基质金属蛋白酶组织抑制剂1表达失衡有关。
배경：기질금속단백매조직억제제1시여기질금속단백매13상대응적길항제，량자간표체수평화공능활성적평형대세포외기질적대사상태기착중요작용，단재 DH 돈서골관절염발생발전과정중，량자표체수평，우기량자표체수평비치적변화상불명학。 　　목적：탐토불동월령DH돈서관절연골중기질금속단백매13、기질금속단백매조직억제제1표체비치적변화급기여DH돈서증령성원발골성관절염발병과정중연골퇴변정도적관계。 　　방법：선취2，4，8，12월령자성DH각6지，취슬관절관찰관절연골적대체형태후상규탈개、포매、제작석사절편，용우VG염색행조직학관찰，채용Mankin평분계통정량분석관절연골퇴변정황，채용면역조직화학방법검측슬관절연골중기질금속단백매13、기질금속단백매조직억제제1표체정황，응용 Image pro-Plus 6.0연건대면역조직화학양성단백표체정황진행적분흡광도계산。선성회귀분석판단Mankin평분여기질금속단백매13/기질금속단백매조직억제제1비치적상관성。 　　결과여결론：DH 돈서2월령슬관절연골무관절염표현，4월령출현경도연골퇴변，병수월령증가진행성가중，Mankin평분수월령증가축점증고，각조지간적차이균유현저성의의(P <0.05)。기질금속단백매13、기질금속단백매조직억제제1적표체균수월령진행성증가，량자비치여Mankin평분정정상관성(P <0.05)。결과제시DH돈서4월령출현슬관절연골퇴행성변화，수월령증가이진행성가중，기병리개변여기질금속단백매13/기질금속단백매조직억제제1표체실형유관。
BACKGROUND:Tissue inhibitor of matrix metaloproteinase 1 (TIMP-1) is the corresponding antagonist of matrix metaloproteinase 13 (MMP-13), and their balance between expression and functional activity exerts an important role in the metabolic state of the extracelular matrix. During the development of osteoarthritis, however, TIMP-1 and MMP-13 expressions and their expression ratio show unclear changes in DH guinea pigs. OBJECTIVE:To explore the expression levels of MMP-13 and TIMP-1 in DH guinea pigs with different ages, and to analyze the relationship between the ratio of MMP-13 to TIMP-1 and the age-dependent degenerative changes in the articular cartilage. METHODS:Twenty-four female Dunkin Hartley guinea pigs were sacrificed at age of 2, 4, 8, 12 months separately, with six animals at each time point. The knee joints were colected and gross visual appearance of the articular cartilage was observed, then were decalcified and prepared for paraffin sections. VG staining and Mankin score were used to analyze the histological changes. Immunohistochemistry was conducted to assess the expression levels of MMP-13 and TIMP-1 in the cartilage. Integrated absorbance values were used as the quantitive analysis calculated by Image pro-Plus 6.0. Linear regression analysis was done to analysis the relationship between Mankin score and the ratio of MMP-13/TIMP-1. RESULTS AND CONCLUSION:Normal appearance in the articular cartilage was observed in 2-month-old DH guinea pigs, while degenerative changes in the articular cartilage were shown in 4-month-old animals, which became severer with age. Significant difference was found in Mankin score between any two groups (P < 0.05). The ratio of MMP-13 to TIMP-1 increased with age, and the ratio was positively correlated to the Mankin score (P < 0.05). Age-related articular cartilage degeneration occurred in Dunkin Hartley guinea pigs at 4 months of age, and devoloped with age, which is related with the imbanlance of the expression ratio of MMP-13 to TIMP-1.