降钙素对兔膝骨关节炎发病过程中细胞因子及关节软骨细胞凋亡的试验研究

目的探讨降钙素(CT)对兔膝骨关节炎发病过程中细胞因子及关节软骨细胞凋亡情况的影响。方法将36只健康大耳白兔随机分为空白对照组(A组)、模型组(B组)和CT治疗组(C组),B、C两组采用改良Hulth法复制膝骨关节炎模型,A组除切开皮肤和关节腔外,不做其他处理,从术后第6周开始C组每天皮下注射CT 5u/kg,A、B组给与等量生理盐水皮下注射,连续注射20 d后处死动物。观察膝骨关节炎(KOA)发病过程中关节软骨病理组织学的变化,关节液中细胞因子IL-1、TNF-α、NO的变化。关节软骨Ⅱ型胶原及基质金属蛋白酶-1(MMP-1)的变化,以及CT对上述指标的影响。结果与A组相比,B组JP和Mankin’s评分明显升高,关节软骨损伤明显加重,关节液中IL-1、TNF-α、NO含量明显升高(P<0.05),关节软骨Ⅱ型胶原含量明显降低,MMP-1活性和软骨细胞凋亡百分数明显升高(P<0.05);与B组相比,C组关节液中IL-1、TNF-α、NO含量明显降低(P<0.05),关节软骨损伤减轻、Ⅱ型胶原含量明显升高,MMP-1活性和软骨细胞凋亡百分数明显降低(P<0.05)。结论 CT对KOA的治疗作用与细胞因子及细胞外基质合成与分解代谢失衡的恢复有关。

The experimental research of the effects of calcitonin on cytokines and apoptosis of articular chondrocytes during the development of knee osteoarthritis in rabbits

Objective To explore the effects of calcitonin(CT) on cytokines and apoptosis of articular chondrocytes during the development of knee osteoarthritis in rabbits.Methods Thirty-six rabbits were randomly divided into 3 groups: normal group(group A),model group(group B),and CT treatment group(group C).The rabbits in group B and C were made into knee osteoarthritis by modified Hulth’s method.The rabbits in group A were dealt with no procedure except the incision of skin and articular cavity.The rabbits in group C were administered with hypodermic injection of CT everyday(5 U/kg).The other rabbits were administered with normal saline injection.All rabbits were sacrifised after continuous treatment for 20 days.The pathology and apoptosis of articular cartilage,variation of cytokines IL-1,TNF-a,and NO in synovial fluid,collagen type II,and MMP-1,and the effect of CT,were observed.Results The JP and Mankin’s scores of rabbits in group B were significantly higher than those in group A.The articular cartilage injury of rabbits in group B was also severer than that in group A.Meanwhile,the content of IL-1,TNF-α,and NO in synovial fluid significantly increased(P<0.05).The content of collagen type II significantly decreased and MMP-1 activity and the percent of apoptotic articular chondrocytes significantly increased(P<0.05).Comparing to group B,the content of IL-1,TNF-α,and NO in synovial fluid of rabbits significantly decreased(P<0.05),the articular cartilage injury reduced and the content of collagen type II significantly increased,and MMP-1 activity and the percent of apoptotic articular chondrocytes significantly decreased(P<0.05),in group C.Conclusion The efficacy of CT on KOA may be related to the recovery of the imbalance of both cytokines and synthesis-degradation of cartilage matrix.