Objective: To study the effect of Shaoyangzhugu (SYZG) Formula (a formula consisting of 9 traditional Chinese drugs) in delaying the degeneration of articular cartilage and the role p19Arf-p53-p21Cip1 signaling pathway in mediating this effect.
Method: Thirteen aged cynomolgus monkeys with degenerative knee joints were selected based on X-ray findings, and one of them was randomly selected for pathological observation. The other monkeys were randomized equally into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and saline group. All the monkeys were sacrificed after 8 weeks of treatment with intragastric administration of the drugs or saline. The pathology in the knee joint articular cartilage was observed and the mRNA and protein expressions of p19Arf, p53, and p21Cip1 in the articular cartilage were detected using RT-qPCR and Western blotting.
Results: The pathological findings of the articular cartilage in old cynomolgus monkeys were consistent with the characteristics of knee osteoarthritis (KOA). Mankin scores of the cynomolgus monkeys were 7.38∓0.52 in SYZG Formula group, 7.88∓0.83 in ammonia moxime group, and 8.38∓0.74 in saline group, showing a significant difference between SYZG Formula group and saline group (P<0.05). The expressions of p19Arf, p53, and p21Cip1 were the lowest in SYZG Formula group and the highest in saline group with significant differences among the 3 groups (P<0.05).
Conclusion: SYZG Formula can delay chondrocyte senescence by regulating p19Arf-p53-p21Cip1 signaling pathway to delay articular cartilage degeneration in aged cynomolgus monkeys.
目的: 根据“少阳主骨”理论，研究少阳主骨方介导p19Arf-p53-p21Cip1信号通路调控关节软骨退变的机制。
方法: 通过X线选取13只膝关节退变的老年食蟹猴，随机选取1只进行病理学观察，其余食蟹猴随机分为少阳主骨方组、氨糖美辛组、生理盐水组，每组4只，连续灌胃8周后处死所有食蟹猴，取关节软骨进行病理学观察，RT-qPCR、Western blot检测关节软骨中p19Arf、p53、p21Cip1基因与蛋白的表达。
结果: 老年食蟹猴KOA模型关节软骨符合KOA病理变化，3组食蟹猴Mankin评分少阳主骨方组7.38±0.52分、氨糖美辛组7.88±0.83分、生理盐水组8.38±0.74分，少阳主骨方组与生理盐水组间具有统计学差异（P < 0.05）；p19Arf、p53、p21Cip1基因与蛋白的表达少阳主骨方组 < 氨糖美辛组 < 生理盐水组，具有统计学差异（P < 0.05）。
结论: 少阳主骨方可以延缓关节软骨退变，调控p19Arf-p53-p21Cip1表达。