AMD3100体内干预SDF-1/CXCR4信号通路对关节软骨组织退变的影响

The Influence of AMD3100 Intervention to the SDF-1/CXCR4 Signaling Pathway on Articular Cartilage Degeneration in Vivo

目的:探讨趋化因子受体4(chemokine receptor 4,CXCR4)特异性拮抗剂AMD3100体内干预SDF-1/CXCR4信号通路对关节软骨组织退变的影响。方法:取6月龄雄性Hartley豚鼠36只随机分成3组,每组12只。A组(实验组):每只背部皮下植入Alzet微量泵,内含PBS液稀释过的AMD3100,每天以180μg/ml的浓度泵入;B组(实验对照组):每只皮下植入Alzet微量泵,内含PBS液;C组(空白对照组):不做任何处理。常规饲养至12周后处死Hartley豚鼠,取下双膝关节软骨,对膝关节软骨组织块行HE、番红染色,采用Mankin组织学评分,免疫组化检测软骨组织中IL-1、TNF-α的表达。结果:HE及番红染色结果:实验组比实验对照组和空白对照组的软骨退变程度轻,实验组Mankin组织学评分结果低,差异有统计学意义(P<0.05)。免疫组化检测结果:实验组较实验对照组和空白对照组的IL-1、TNF-α表达量低,差异有统计学意义(P<0.05)。结论:AMD3100可体内干预SDF-1/CXCR4信号通路,阻断SDF-1与软骨组织表面的CXCR4受体结合,减轻软骨组织的退变。

Objective To explore the influences of chemokine receptor 4（CXCR4） specific antagonist AMD3100 intervention to the SDF-1/CXCR4 signaling pathway on the articular cartilage degeneration.Methods 36 male Hartley guinea pigs（6 months old）were divided into groups A,B,and C randomly. Alzet trace pump was implanted in the back subcutaneous tissue of pigs in group A（experimental group）and the liquid containing PBS diluted AMD3100 with concentration of 180ug/ml was pumped in every day. Alzet trace pump was also implanted in the back subcutaneous tissue of pigs in group B（control experimental group）and PBS was pumped in every day. Gigs in group C（blank group）received no any treatment. All the pigs were sacrificed after 12-week conventional breeding and the cartilage of both knees was removed immediately. The cartilage tissue structure was examined with HE and Safranin staining. The Mankin score was used to evaluate the histological changes,immunohistochemistry to detect the expression of IL- 1 and TNF alpha. Results The cartilage degeneration was lesser,and the expressions of IL-1 and TNF alpha and the Mankin score was lower in group A than in groups B and C. Conclusion AMD3100 could intervene the SDF-1/CXCR4 signaling pathway, and block the binding of SDF-1 to the CXCR4 receptor on the surface of the cartilage tissue, and thus decrease the cartilage degeneration.