目的:考察穿山龙总皂苷(total saponins from rhizoma Dioscoreae nipponicae,RDN)对痛风性关节炎大鼠关节炎滑膜IL-1β及其介导的信号转导通路的影响。方法:40只雄性Wistar大鼠随机分为四组,分别为正常组、模型组、穿山龙总皂苷低(40mg/kg)、高剂量组(160mg/kg),连续灌胃穿山龙总皂苷5天。第3d灌胃穿山龙总皂苷1h后,膝关节上方髌上韧带进针,注射0.2ml浓度为25mg/ml的微晶尿酸钠结晶混悬液到关节腔,造成实验性痛风性关节炎模型。采用HE和伊红染色观察关节滑膜组织病理学变化,免疫组化法检测穿山龙总皂苷对大鼠膝关节滑膜组织中IL-1B、SDF-1、cxCR4、P13K、PKC和NF-κB表达的影响。结果:与正常组比较,模型组大鼠膝关节滑膜组织中IL-1B、SDF-1、CXCR4、P13K、PKC和NF-κB表达水平显著升高(0.087±0.021,0.064±0.017,0.146±0.042,0.139±0.057,0.088±0.021,0.079±0.018),穿山龙总皂苷低剂量组能显著降低CXCR4表达水平(0.081±0.006)。穿山龙总皂苷高剂量组能显著降低IL-113、CXCR4、P13K、PKC和NF-κB表达水平(0.035±0.007,0.104±0.011,0.077±0.017,0.039±0.011,0.030±0.009)。结论:穿山龙总皂苷可抑制IL-1β及其介导的信号转导通路;穿山龙总皂苷具有治疗痛风性关节炎(Gouty Arthritis,GA)的潜在价值。
Objective: To study the influence of total saponins from rhizoma Dioscoreae nipponicae on IL-1β expression and the signal pathway which it regulated in synovium of joint in rats of gouty arthritis. Methods: 40 SPF Wistar rats were randomly divided into four groups. They were normal group, model group and total saponins groups of low (40mg/kg) and high(160mg/kg) doses. Total saponins of RDN were given for 5 successive days. An hour after total saponins of RDN were given at the 3d, 0.2 m125mg/ml MSU suspension was injected into articular cavity through anadesma of kneecap in the knee-joint to induce model of gouty arthritis. The pathological changes in synovium of joint were detected by HE and eosin dying. IL-1β,SDF-1, CXCR4, PI3K, PKC and NF-κB expression in synovium of joint in rats of gouty arthritis were detected by immunohistochemical method. Result: IL-1β, SDF-1, CXCR4, PI3K, PKC and NF-KB expressions in synovium of joint in the model group were increased significantly when compared with the normal group(0.087 ±0. 021,0.064±0.017,0. 146 ±0.042,0. 139 ±0. 057,0. 088 ± 0. 021 and 0.079 ± 0.018) ( P 〈 0.05 ). Total saponins from Rhizoma Dioscoreae nipponicae of low dose could reduce the expression levels of CXCR4 significantly(0.081±0. 006) ( P 〈 0.01 ). Total saponins from Rhizoma Dioscoreae nipponicae of high dose could reduce the expression levels of IL-1β,CXCR4,PI3K,PKC and NF-KB significantly(0. 035±0.007,0. 104±0.011,0.077 ±0.017,0.039 ±0.011 and 0. 030±0. 009) (P 〈0.05 ). Conclusion: Total saponins from rhizoma Dioscoreae nipponicae could inhibit expression of IL-1β and the signal pathway which it regulated. Total saponins of RDN may provide a new therapeutic approach in treatment of gouty arthritis.