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 with-drawal 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。
Therapeutic effect and mechanism of Salvia miltiorrhiza polysaccharide on sodium iodoacetate-induced knee osteoarthritis rats
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 sodi-um 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.Chan-ges 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 im-proved,as evidenced by a significant decrease in the Markin score(P＜0.05,P＜0.01).Furthermore,levels of cartilage oli-gomeric 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 car-tilage 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 phos-phorylated 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.
Salvia miltiorrhiza polysaccharidebone metabolismapoptosismitogen-activated protein kinase/nuclear factor-κB signaling pathwayknee osteoarthritis
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