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目的:观察木瓜三萜对佐剂性关节炎(adjuvant arthritis,AA)大鼠关节滑膜组织中Akt,核转录因子-κB(NF-κB)和炎症因子表达影响,在此基础上探讨其可能机制。方法:80只雄性SD大鼠随机分为正常组、模型组、木瓜总三萜中、高剂量组(50,100 mg·kg~(-1)),除正常组外,其余大鼠右后足跖注射弗氏佐剂造模,木瓜三萜(50,100 mg·kg-1)灌胃(ig)给药,足容积法测量致炎侧足肿胀、进行关节评分;光学显微镜观察关节滑膜病理变化;酶联免疫吸附测定(ELISA)法检测大鼠关节滑膜组织中肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)和白细胞介素-8(IL-8)含量,蛋白质免疫印迹法(Western blot)检测关节滑膜组织中蛋白激酶B(Akt),磷酸化蛋白激酶B(p-Akt)和人核转录因子-κB p65(NF-κB p65)表达水平。结果:与正常组比较,大鼠致炎后14 d关节肿胀度达峰值,可见模型组关节滑膜组织炎症反应,如滑膜组织增生,炎细胞浸润;关节组织中TNF-α,IL-1β,IL-6和IL-8含量明显上升,p-Akt和NF-κB p65表达增多(P<0.01);与模型组比较,木瓜三萜中、高剂量组能显著抑制AA大鼠足爪肿胀、降低多发性关节评分及改善关节滑膜组织病理变化,降低滑膜组织病理评分,降低关节滑膜组织中TNF-α,IL-1β,IL-6和IL-8含量及p-Akt和NF-κB p65蛋白表达水平(P<0.05,P<0.01)。结论:木瓜三萜具有显著的抗炎作用,抑制Akt/NF-κB信号通路激活及促炎因子生成可能是其发挥抗炎作用的重要机制之一。
Objective: To observe the effect of papaya triterpenoid on the expression of Akt, NF-κB and inflammatory cytokines in synovial tissue of adjuvant arthritis (AA) rats. mechanism. Methods: Eighty male Sprague-Dawley rats were randomly divided into normal group, model group and high dose group (50,100 mg · kg -1) of papaya total triterpene. Except normal group, The rats were injected intragastrically with Freund’s adjuvant (50,100 mg · kg-1) after administration of Freund’s adjuvant. The foot volume was used to measure the swelling of the inflamed side and the joints were scored. The pathological changes of the synovium were observed with light microscopy. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and synovial fluid in synovial tissue of rats were detected by enzyme linked immunosorbent assay (ELISA) IL-8 and Western blot were used to detect the protein expressions of Akt, p-Akt and NF-κB in synovial tissue, p65 (NF-κB p65) expression levels. Results: Compared with the normal group, the degree of swelling in the joint reached its peak on the 14th day after inflammation, showing the synovial tissue inflammatory response in the model group, such as synovial tissue proliferation and inflammatory cell infiltration. The levels of TNF-α and IL-1β , IL-6 and IL-8 levels increased significantly, p-Akt and NF-κB p65 expression increased (P <0.01); compared with the model group, papaya triterpenoid medium and high dose group can significantly inhibit the paw swelling of AA rats , Reduce multiple joint score and improve synovial tissue pathological changes, reduce synovial histopathological score, reduce synovial tissue TNF-α, IL-1β, IL-6 and IL-8 content and p-Akt and NF -κB p65 protein expression (P <0.05, P <0.01). Conclusion: The triterpene papaya has a significant anti-inflammatory effect. Inhibiting the activation of Akt / NF-κB signaling pathway and the production of proinflammatory cytokines may play an important role in anti-inflammatory effects.