伸筋草生物碱对佐剂性关节炎大鼠的抗炎作用及机制研究

Anti-inflammatory effect and mechanism of shenjincaoalkaloids on adjuvant arthritis rats

目的探讨伸筋草生物碱对完全弗氏佐剂(CFA)诱导大鼠关节炎的治疗作用及机制。方法健康SD大鼠48只,随机分为6组,每组8只,即对照组、模型组、依托考昔片(阳性药,1 mg/kg)组及伸筋草生物碱低、中、高剂量(30、60、120 mg/kg)组,除对照组外,其余40只大鼠sc 0.1 mL CFA造模,致炎15 d后,连续ig给药30 d。测定大鼠足趾肿胀率、HE染色后观察造模测踝关节滑膜病理改变;致炎45 d,ELISA法测定血清中白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平。结果与模型组比较,依托考昔片及伸筋草生物碱低、中、高剂量组足趾肿胀率均显著下降(P<0.05、0.01);中、高剂量伸筋草生物碱明显改善滑膜细胞、巨噬细胞、纤维细胞增生与炎症细胞浸润;与模型组比较,依托考昔片及伸筋草生物碱高剂量组大鼠血清TNF-α水平显著下降(P<0.05),依托考昔片及伸筋草生物碱各剂量组IL-1β水平均显著降低(P<0.01)。结论伸筋草生物碱显著抑制CFA诱导关节炎大鼠关节肿胀,改善大鼠踝关节滑膜病变,其作用机制可能与降低体内IL-1β、TNF-α水平有关。

Objective To explore the therapeutic effect and mechanism of shenjincao alkaloids(SJA)on arthritis induced by complete freund’s adjuvant(CFA)in rats.Methods 48 healthy SD rats were randomly divided into 6 groups,8 in each group,namely control group,model group,Etoncoxib(Positive drug,1 mg/kg)group,and low-,medium-and high-dose(30,60,and 120 mg/kg)SJA groups,40 healthy SD rats were injected with 0.1 mL CFA in addition to control group.The swelling rate of rat toes was measured and the pathological changes of ankle synovial membrane were observed.For 45 days,ELISA assay was used to determine the level of serum IL-1βand TNF-α.Results Compared with model group,the toe swelling rate of each group was significantly decreased(P<0.05 and 0.01),and the levels of synovial cells,macrophages,fibroblast proliferation and inflammatory cell infiltration were also significantly decreased in medium and high doses of SJA groups.Compared with model group,the serum TNF-αlevel of rats in Etoncoxib and high-dose group of SJA decreased significantly(P<0.05),and the IL-1βlevel of rats in Etoncoxib and each dose group of SJA decreased significantly(P<0.01).Conclusion SJA can inhibit the CFA induced joint swelling in arthritis rats,improve ankle synovial lesions in rats,and have therapeutic effects on adjuvant arthritis rats.The mechanism may be related to decreasing the level of IL-1βand TNF-αin vivo.