穿山龙总皂苷对痛风性关节炎大鼠关节炎滑膜IL-1β及其信号转导通路的影响

Effects of total saponins from rhizoma Dioscoreae nipponicae on expression of IL-1β and the signal pathway which is regulated in synovium of joint in rats of gouty arthritis

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-1β、SDF-1、CXCR4、PI3K、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-1β、SDF-1、CXCR4、PI3K、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-1β、CXCR4、PI3K、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.