关节腔注射羧甲基壳聚糖预防膝骨关节炎软骨退变

The experimental study of intra-articular carboxymethylated chitosan injection for the prevention of cartilage degeneration of osteoarthritis in knees

目的观察羧甲基壳聚糖(CMCTS)关节腔注射对骨关节炎(OA)模型关节软骨退变及软骨基质金属蛋白酶(MMP-1,-3)及其组织抑制物(TIMP-1)mRNA表达的影响。方法32只大耳白兔行单膝前交叉韧带切断术,随机分为A^D组,A、B组分别于术后立即关节腔注射高、低分子量2%CMCTS 0.3 ml,每2周1次;C组术后立即关节腔注射1%透明质酸钠(SH)0.3 ml,每周1次;D组术后不注射任何药物。术后6周处死动物,比较各组股骨内髁关节软骨的大体变化,采用逆转录聚合酶链反应(RT-PCR)方法检测软骨MMP-1,-3及TIMP-1 mRNA的表达水平。

Objective To observe the influence of intra-articular injection of carboxymethylated ehitosan （CMCTS） on cartilage degeneration and mRNA expression of matrix metalloproteinase-1,-3 （MMP-1, -3） and tissue inhibitor of metalloproteinase-1 （ TIMP-1） in cartilage of osteoarthritis （OA） model. Methods Thirty-two white rabbits underwent unilateral anterior cruciate ligament transection （ACLT） and divided into A-D groups. The rabbits in group A received 0.3 ml of intra-articular 2 % high molecular weight （MW） CMCTS injection immediately after surgery, once two weeks, those in group B were treated under the same conditions using low MW CTCTS and those in group C received 0.3 ml of intra-articular 1% sodium hyaluronate （SH） injection immediately after surgery, once a week. Animals in group D were not injected after ACLT. At 6th week after surgery, the rabbits were sacrificed. The cartilage changes on the medial femoral condyles were graded separately. Gene expression of MMP-1, -3 and TIMP-1 was detected by using reverse transcription-polymerase chain reaction （RT-PCR）. Results Cartilege degeneration in untreated group was significantly more severe than that in CMCTS and SH injection groups. In cartilage, the expression of MMP-1 and MMP-3 mRNA was suppressed in the CMCTS injection groups and there was no significant difference between high and low MW CMCTS injection groups. No difference in MMP-1 and MMP-3 expression was found between SH injection group and untreated group. No difference in TIMP-1 expression was observed in cartilage among the groups. Conclusion CMCTS could significantly downregulate the mRNA expression of MMP-1,-3 and reduce severity of cartilage degradation. CMCTS may have a protective effect on articular cartilage.