大豆皂苷缓解骨关节炎模型大鼠软骨损伤和关节炎症的机制

Soyasaponins alleviate cartilage damage and joint inflammation of osteoarthritis rats

目的探究大豆皂苷缓解骨关节炎模型大鼠软骨损伤和关节炎症的可能机制。方法SD大鼠随机分为假手术组、模型组、大豆皂苷低剂量组(20 mg·kg^(-1))、大豆皂苷中剂量组(40 mg·kg^(-1))、大豆皂苷高剂量组(80 mg·kg^(-1))和双醋瑞因组(54 mg·kg^(-1)),每组15只;切断前交叉韧带的方式构建骨性关节炎模型。HE和番红氧固绿染色观察关节滑膜组织病理损伤并进行Mankin's评分和OARSI评分,酶联免疫吸附测定(ELISA)检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平,Western blot检测丝裂原激活蛋白激酶(MAPK)、转录因子核因子κB(NF-κB)、NOD样受体家族蛋白3(NLRP3)、凋亡相关微粒蛋白(ASC)、半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)蛋白表达。结果与模型组比较,大豆皂苷(中、高)剂量组和双醋瑞因组大鼠软骨组织表面较光滑,Mankin's、OARSI评分降低,血清及关节液中TNF-α、IL-1β、IL-6水平降低,p-p38 MAPK/p38 MAPK、p-NF-κB p65/NF-κB p65、NLRP3、ASC、Caspase-1表达降低(P<0.05),且具有剂量效应(P<0.05)。结论大豆皂苷可缓解骨关节炎大鼠软骨组织损伤及关节炎症损伤,其机制可能与抑制MAPK/NF-κB信号通路和NLRP3炎症小体活化有关。

This study was performed to explore the possible mechanism of soyasaponins alleviating cartilage damage and joint inflammation in osteoarthritis rats.In the experiment,SD rats were recruited and randomly divided into sham operation group,model group,low-dose,medium-dose and high-dose soyasaponins groups(20,40,80 mg·kg^(-1)),and diacerein group(54 mg·kg^(-1)),with 15 rats in each group.The osteoarthritis model was constructed by resection of anterior cruciate ligament.The pathological damage of synovial tissues was observed by HE and safranin fast green staining;Mankin's scoring and OARSI scoring were conducted;the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expressions of mitogen-activated protein kinase(MAPK),nuclear factorκB(NF-κB),nucleotide-binding oligomerization domain-like receptors 3(NLRP3),apoptosis-related microparticle protein(ASC)and cysteine aspartate protease-1(Caspase-1).Data showed that compared with model group,medium-dose and high-dose soyasaponins groups and diacerein group demonstrated smoother surface of cartilage tissues,lower levels of Mankin's and OARSI scores,lower levels of TNF-α,IL-1βand IL-6 in serum and joint fluid,lower expression of p-p38 MAPK/p38 MAPK,p-NF-κB p65/NF-κB p65,NLRP3,ASC and Caspase-1(P<0.05),and there was dose effects(P<0.05).In conclusion,soyasaponins can alleviate cartilage tissue damage and joint inflammation damage in osteoarthritis rats,which may be related to inhibiting MAPK/NF-κB signaling pathways and NLRP3 inflammasome activation.