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目的:观察马钱子总碱囊泡凝胶对佐剂性关节炎(AA)大鼠的治疗作用及其机制。方法:SD大鼠随机分为9组:正常组、AA模型组、马钱子总碱囊泡凝胶高、中、低剂量(25,12.5,6.25 mg·kg-1)组、马钱子总碱药物凝胶高、中、低剂量(25,12.5,6.25 mg·kg-1)组和扶他林对照组(双氯芬酸二乙胺乳胶剂,50 mg·kg-1)。除正常组外,其余各组均以弗氏完全佐剂(FCA)每鼠左后足跖皮内注射0.1 mL致炎,各给药组在大鼠足趾部分均匀涂抹药物并用油纸包裹。足容积法测量继发侧足肿胀度,进行疼痛评分和多发性关节炎评分,HE染色观察关节病理损伤,酶联免疫吸附测定法(ELISA)测定白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、前列腺素(PGE2)、白细胞介素6(IL-6)和血管内皮细胞生长因子(VEGF)的表达。结果:与模型组相比,囊泡凝胶和药物凝胶可明显减轻AA大鼠的继发侧足爪肿胀度(17~21 d)。马钱子总碱囊泡凝胶和药物凝胶可有效抑制大鼠多发性关节炎指数,减轻关节病理学损伤,马钱子总碱囊泡凝胶还可降低滑膜组织匀浆上清液IL-1,TNF-α,PGE2,IL-6水平和提高VEGF水平。结论:马钱子总碱囊泡凝胶可拮抗大鼠AA发展,其作用机制与抑制炎症介质的生成密切相关。
Objective: To observe the therapeutic effect and mechanism of Strychnos calco capsulate on adjuvant arthritis (AA) rats. Methods: The SD rats were randomly divided into 9 groups: normal group, AA model group, Strychnos total vesicle gel in high, medium and low dose groups (25, 12.5 and 6.25 mg · kg -1) Total alkaloids gel was treated with high, medium and low doses of 25,12.5 and 6.25 mg · kg -1 groups and fondaparinux group (diclofenac diethylamine emulsion, 50 mg · kg -1). Except for normal group, intradermal injection of 0.1 mL intradermal injection of complete Freund’s adjuvant (FCA) resulted in inflammation of the left hind paw. Rats in each group were uniformly coated with oil and wrapped in oil paper. Foot volume method was used to measure the extent of secondary side-foot swelling. The pain scores and multiple arthritis scores were measured. The pathological changes of joints were observed by HE staining. The levels of interleukin-1 (IL-1) and tumor necrosis were determined by enzyme linked immunosorbent assay (ELISA) (TNF-α), prostaglandin (PGE2), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) RESULTS: Compared with the model group, vesicle gel and drug gel significantly reduced the degree of secondary side-foot swelling in AA rats (17-21 days). Strychnos total vesicle gel and drug gel can effectively inhibit the rat multiple arthritis index, reduce the pathological injury of the joint, Strychnos total vesicle gel can also reduce the synovial tissue homogenate supernatant IL-1, TNF-α, PGE2, IL-6 and increase the level of VEGF. Conclusion: Strychnos total vesicle gel can antagonize the development of rat AA and its mechanism of action is closely related to inhibition of inflammatory mediators.