丹参多糖对碘乙酸钠所致大鼠膝骨性关节炎的治疗作用及机制研究

Therapeutic effect and mechanism of Salvia miltiorrhiza polysaccharide on sodium iodoacetate-induced knee osteoarthritis rats

探讨丹参多糖对碘乙酸钠所致大鼠膝骨性关节炎(knee osteoarthritis,KOA)的治疗作用及潜在机制。采用膝关节腔内注射碘乙酸钠法建立大鼠KOA模型,分为模型组、丹参多糖低、高剂量组(40、80 mg/kg)及塞来昔布组(20 mg/kg),另选取12只大鼠作为假手术组,持续干预4周后检测相关指标变化情况。结果发现,与模型组比较,丹参多糖低、高剂量组大鼠爪压评分及步态评分明显下降(P<0.05,P<0.01),机械性缩足反射阈值(mechanical withdrawal threshold,MWT)及热缩足反射潜伏期(thermal withdrawal latency,TWL)明显增加(P<0.01),关节软骨组织病理形态减轻,Markin评分明显降低(P<0.05,P<0.01);血清软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)、血清Ⅰ型胶原C末端肽(C-terminal peptide of type I collagen,CTX-Ⅰ)含量及关节软骨组织半胱氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤-2(B-lymphoblastoma-2,Bcl-2)相关X蛋白(Bcl-2 associated X protein,Bax)mRNA表达明显下降(P<0.05,P<0.01),骨钙素(osteocalcin,OCN)含量及关节软骨组织Bcl-2 mRNA表达明显升高(P<0.05,P<0.01),关节滑液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6含量及关节软骨组织磷酸化丝裂原活化蛋白激酶p38(phosphorylated mitogen-activated protein kinase p38,p-p38 MAPK)、磷酸化核因子-κB p65(phosphorylated nuclear factor-κB p65,p-NF-κB p65)蛋白表达明显降低(P<0.05,P<0.01)。研究结果表明,丹参多糖对碘乙酸钠所致大鼠KOA具有治疗作用,其机制与改善骨代谢、抗凋亡及抑制MAPK/NF-κB信号通路介导的炎症反应有关。

This study aims to investigate the therapeutic effect and potential mechanism of Salvia miltiorrhiza polysaccharide(SMP)on sodium iodoacetate-induced knee osteoarthritis(KOA)rats.The rat model of KOA was induced by injecting sodium iodoacetate into the knee joint.The rats were divided into a model group,low-dose and high-dose SMP groups(40 and 80 mg/kg),and a celecoxib group(20 mg/kg).Additionally,another 12 rats were selected as the sham operation group.Changes in relevant indexes were assessed after four weeks of continuous intervention.The results indicated that compared to the model group,rats in both low-dose and high-dose SMP groups exhibited a significant decrease in paw pressure score and gait score(P<0.05,P<0.01).Additionally,mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were significantly increased(P<0.01).The study also found that the pathological morphology of articular cartilage improved,as evidenced by a significant decrease in the Markin score(P<0.05,P<0.01).Furthermore,levels of cartilage oligomeric matrix protein(COMP)and C-terminal peptide of type I collagen(CTX-I)in serum,as well as mRNA expressions of Caspase-3 and B-lymphoblastoma-2(Bcl-2)associated X protein(Bax)in articular cartilage were significantly decreased(P<0.05,P<0.01).On the other hand,osteocalcin(OCN)content in serum and Bcl-2 mRNA expression in articular cartilage were significantly increased(P<0.05,P<0.01).Moreover,the study observed a significant decrease in the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in synovial fluid,along with reduced expressions of phosphorylated mitogen-activated protein kinase p38(p-p38 MAPK)and phosphorylated nuclear factor-κB p65(p-NF-κB p65)in articular cartilage(P<0.05,P<0.01).These results indicated that SMP had a therapeutic effect on sodium iodoacetate-induced KOA in rats.This effect was achieved through the improvement of bone metabolism,anti-apoptotic properties,and the inhibition of inflammation via the MAPK/NF-κB signaling pathway.