| 庞琳烜,李 颖,李治琴,杜望磊,谢荣华,丁 进.保护素DX对类风湿关节炎大鼠模型中PI3K/AKT/mTOR信号通路的影响[J].,2023,(3):401-406 |
| 保护素DX对类风湿关节炎大鼠模型中PI3K/AKT/mTOR信号通路的影响 |
| Effects of Protectin DX on PI3K/AKT/mTOR Signaling Pathway in a Rat Model of Rheumatoid Arthritis |
| 投稿时间：2022-07-28 修订日期：2022-08-24 |
| DOI：10.13241/j.cnki.pmb.2023.03.001 |
| 中文关键词: 类风湿关节炎 保护素DX B淋巴细胞 Th1/Th2失衡 PI3K/Akt/mTOR信号通路 |
| 英文关键词: Rheumatoid arthritis Protectin DX B lymphocytes Th1/Th2 imbalance PI3K/Akt/mTOR signaling pathway |
| 基金项目:国家自然科学基金项目（81701617） |
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| 中文摘要: |
| 摘要 目的：研究保护素DX（PDX）对类风湿关节炎（RA）大鼠模型的治疗作用及机制，及其对PI3K/AKT/mTOR信号通路的影响。方法：通过皮下注射牛Ⅱ型胶原与弗氏完全佐剂诱导RA大鼠模型，建模后将SD大鼠随机分为4组：对照组（n=12）：正常SD大鼠；RA组（n=12）：RA模型大鼠；低剂量PDX处理组（n=12，L-PDX组）：接受10 μg/kg/d PDX治疗的RA模型大鼠；高剂量PDX处理组（n=12，H-PDX）：接受20 μg/kg/d PDX治疗的RA模型大鼠。各组大鼠治疗4周后，采用ELISA法检测血清中IgA、IgG、IgM、TNF-α、IFN-γ、IL-4和IL-10的水平。通过苏木精伊红（HE）染色评价大鼠踝关节病变。通过免疫组化染色或Western blot检测滑膜组织中PI3K、p-PI3K、AKT、p-AKT、mTOR、p-mTOR、Bcl-2、Bax、LC3-I、LC3-II和Becline-1的表达。结果：与RA组相比，L-PDX组和H-PDX组的关节炎指数（AI）评分均显著降低（P<0.05），炎性细胞浸润、软骨破坏程度及滑膜上皮细胞增生减轻。与RA组相比，L-PDX组和H-PDX组的血清IgA、IgG和IgM含量均降低（P<0.05）。与RA组相比，L-PDX组和H-PDX组的血清TNF-α和IFN-γ水平均降低，IL-4和IL-10水平均升高（P<0.05）。与RA组相比，L-PDX组和H-PDX组大鼠踝关节滑膜组织中的p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR和Bcl-2的蛋白相对表达量均降低，而Bax、LC3-II/LC3-I和Becline-1的蛋白相对表达量均升高（P<0.05）。结论：本研究表明PDX可有效减轻RA大鼠症状，其机制与调节B淋巴细胞活化和体液免疫、纠正Th1/Th2失衡、抑制PI3K/Akt/mTOR信号通路有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the therapeutic effect and mechanism of protectin DX (PDX) on rheumatoid arthritis (RA) rat model, and its effect on PI3K/AKT/mTOR signaling pathway. Methods: The RA rat model was induced by subcutaneous injection of bovine type Ⅱ collagen and Freund's complete adjuvant. After modeling, SD rats were randomly divided into 4 groups: Control group (n=12): normal SD rats, RA group (n=12): RA model rats, low-dose PDX group (L-PDX, n=12): RA model rats treated with 10 μg/kg/d PDX, high-dose PDX group (H-PDX, n=12): RA model rats treated with 20 μg/kg/d PDX. After 4 weeks of treatment, the serum levels of IgA, IgG, IgM, TNF-α, IFN-γ, IL-4 and IL-10 were detected by ELISA. Rat ankle joint lesions were evaluated by hematoxylin and eosin (HE) staining. The expressions of PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR, Bcl-2, Bax, LC3-I, LC3-II and Becline-1 in synovial tissue were detected by immunohistochemical staining or Western blot. Results: Compared with RA group, the arthritis index (AI) scores of L-PDX group and H-PDX group were significantly decreased (P<0.05), and the infiltration of inflammatory cells, the degree of cartilage destruction and the proliferation of synovial epithelial cells were reduced. Compared with RA group, the serum IgA, IgG and IgM contents in L-PDX group and H-PDX group were all decreased (P<0.05). Compared with RA group, the serum levels of TNF-α and IFN-γ in L-PDX group and H-PDX group were decreased, and the levels of IL-4 and IL-10 were increased (P<0.05). Compared with RA group, the relative protein expressions of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR and Bcl-2 in the synovial tissue of the ankle joint of the rats in L-PDX group and H-PDX group were decreased, while the relative protein expressions of Bax, LC3-II/LC3-I and Becline-1 were increased (P<0.05). Conclusion: This study shows that PDX can effectively alleviate the symptoms of RA rats, and its mechanism is related to regulating B lymphocyte activation and humoral immunity, correcting Th1/Th2 imbalance, and inhibiting PI3K/Akt/mTOR signaling pathway. |
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