电脉冲介导hIL-10基因转移治疗骨关节炎的实验研究

Electric pulse mediated gene therapy of intramuscular injection hIL-10 plasmid on osteoarthritis

目的 研究电脉冲介导人白细胞介素10裸质粒肌肉注射对骨关节炎的治疗作用。方法 兔右膝关节髌旁内侧切口,行内侧半月板切除术制作骨关节炎模型,4周后按分组于右侧股四头肌注射pcDI或pcDI-IL10质粒,然后立即于注射部位施以电压200v(电极间距离为1cm),波宽40ms,脉冲次数6次和频率1Hz的电脉冲。共注射2次,每次间隔2周。按分组情况分别于术后4周、8周处死动物,行解剖显微镜观察及关节软骨、滑膜病理检查。结果 pcDI-IL10质粒注射组的关节软骨破坏程度较注射pcDI组轻(P<0.01),而较4周处死组稍重。结论 电脉冲介导肌肉pcDI-IL10转移可以延缓骨关节炎的发展。

Objective To investigate the therapeutic effects of intramuscular injection IL-10 plasmid on experimental osteoarthritis of rabbits. Methods A meniscectomy of right knee was performed on the rabbits through a medial parapatellar incision. The rabbits were divided into three experimental groups. Group 1 received no treatment. Group 2 received two consecutive intramuscular injections at two-week intervals of 0.9% saline containing a DNA plasmid, pcDI. Group 3 received two consecutive intramuscular injections at two-week intervals of 0.9% sline containing a DNA plasmid, pcDI-IL10. Soon after the injection, electric pulse was given to the injection site with the parameter of 200 V, 40 ms, 6 pulse and 1 Hz. The injections were given starting 4 weeks post-surgery. The severity ot macroscopic and microscopic changes on cartilage on the medial and femoral condyles and tibial plateaus and synovium were graded separately. RT-PCR was used to detect IL-10 gene transcription in the injection position of the muscle. Results A significant reduction in the width of osteophytes and size of macroscopic lesions (P<0.01) was observed. A reduction was also noted in the severity of histologic cartilage lesions (P<0.01) in the group that received injection of pcDI-IL10 plasmid. Conclusion Intramuscular injection IL-10 plasmid with electric pulse canretard the progression of osteoarthritis, but can not interdict the developarent of the disease.