PDTC关节腔注射对兔创伤性OA软骨MMP-1、MMP-9 mRNA表达的影响

Effects of Intra-articular Injection of Pyrrolidine Dithiocarbamate on mRNA expressions of MMP-1 and MMP-9 in the Cartilage of Rabbits with traumatic osteoarthritis

目的:观察吡咯烷二硫代氨基甲酸酯(PDTC)关节腔注射对兔创伤性骨关节炎(os-teoarthritis,OA)软骨中基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-9(MMP-9)mRNA表达及NF-κBp65活性的影响,探讨PDTC对兔创伤性OA软骨退变进程的影响。方法:取20只新西兰兔行右膝横断前交叉韧带术(ACLT),术后1周随机分为对照组和PDTC组,每组10只。PDTC组关节腔注射PDTC2mg(/只.次),每周2次,连续8周,对照组同一时间点关节腔注射等容量生理盐水。末次用药3天后处死白兔,解剖显微镜下观察股骨内髁软骨的形态学变化,逆转录聚合酶链反应(RT-PCR)检测股骨内髁软骨中MMP-1、MMP-9mRNA表达量,免疫组化检测股骨内髁软骨中NF-κBp65蛋白表达。结果:形态学示PDTC组软骨退变明显轻于对照组(P<0.05),RT-PCR示PDTC组MMP-1、MMP-9mRNA表达量均低于对照组(P<0.01),免疫组化示PDTC组NF-κBp65活性系数明显低于对照组(P<0.01)。结论:PDTC关节腔注射可能通过阻断创伤性OA软骨中NF-κB激活,进而抑制MMP-1、MMP-9mRNA表达,发挥软骨保护作用。

Objective：To observe the effects of intra-articular injection of pyrrolidine dithiocarbamate（PDTC） on mR- NA expressions of metalloproteinase-1,-9 （MMP-1 and MMP-9）and the activities of nuclear factor-kappaB p65 （NF-κBp65） in the articular cartilage of rabbits with traumatic osteoarthritis （OA）,and to explore the influence of PDTC on cartilage degeneration in traumatic OA. Methods：Twenty New Zealand rabbits underwent anterior cruciate ligament transaction （ACLT） of the right knee and then were divided into two groups. The animals in the PDTC group were injected with PDTC（2mg）in the knees after operation, twice a week for 8 weeks. Rabbits in the control group were treated with normal saline under the same condition. All rabbits were sacrificed in 3 days after the last treatment. Cartilagineus changes of the medial femoral condyles were grossly checked and OA severity was observed under dissecting microscope. The mRNA expressions of MMP-1 and MMP-9 in the cartilage of the medial femoral condyles were assessed by revere transcription-polymerase chain reaction （RT-PCR）. Immunohistochemical and morphometric analyses were adopted to detect the protein expression of NF-κBp65 in the cartilage. Results： Carti- lage degeneration in the PDTC group was significantly slighter than that in the control group （P〈0.05）. The mRNA expressions of MMP-1 and MMP-9 in the PDTC group were significantly lower than those in the control group（P〈 0.01）. The activity coefficient of NF-κBp65 in the PDTC group was significantly lower than that in the control group（P〈0.01）. Conclusion：The intra-articular injection of PDTC can inhibit the mRNA expressions of MMP-1 and MMP-9 by blocking the activities of NF-κB in the cartilage of rabbits with traumatic OA. PDTC may have a pro- teetive effect on articular cartilage in traumatic OA.