表没食子儿茶素没食子酸酯通过调控 BAFF/PI3K/Akt/mTOR 信号通路对胶原诱导关节炎大鼠 B 淋巴细胞的促凋亡作用。
Pro-apoptotic effect of epigallo-catechin-3-gallate on B lymphocytes through regulating BAFF/PI3K/Akt/mTOR signaling in rats with collagen-induced arthritis.
机构信息
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, 230032 Hefei, China.
出版信息
Eur J Pharmacol. 2012 Sep 5;690(1-3):214-25. doi: 10.1016/j.ejphar.2012.06.026. Epub 2012 Jul 1.
To investigate the role of PI3K/Akt/mTOR signaling mediated by B cell-activating factor belonging to the TNF family (BAFF) involved in anti-apoptosis of B lymphocytes in rats with collagen-induced arthritis (CIA) and the regulation of epigallo-catechin-3-gallate (EGCG). Sprague-Dawley rats were immunized to induce CIA. CIA rats were randomly separated into different groups and treated with EGCG (40, 80 mg/kg), Paeoniflorin (100mg/kg) from day 18 to day 38 after immunization. The effects of EGCG on B lymphocytes were evaluated by the levels of BAFF, anti-CII antibody, IgA, IgG and IgM, and the expressions of BAFF receptor, P110δ, p-Akt, mTORC1, Bcl-xL and Bim. B lymphocyte proliferations were analyzed by MTT assay. Apoptosis of B lymphocyte were assayed by flow cytometry. Results showed that, in CIA rats, the levels of BAFF, anti-CII antibody, IgA, IgG and IgM enhanced. BAFF receptor, P110δ, p-AKT, mTORC1 and Bcl-xL were expressed highly, while Bim expression decreased. EGCG (40, 80 mg/kg) and Paeoniflorin decreased the levels of BAFF, anti-CII antibody, IgA, IgG, IgM and the expressions of BAFF receptor, P110δ, p-AKT, mTORC1, Bcl-xL in CIA rats, and increased Bim expression. Further studies showed that EGCG could reduce the expression of P110δ and mTORC1 in vitro. EGCG inhibited B lymphocyte proliferation and induced B lymphocyte apoptosis. In conclusion, BAFF/BAFF receptor might regulate B cell anti-apoptosis through PI3K/Akt/mTOR pathway. EGCG had therapeutic effects on CIA rats, which might be relative to the inhibition effects of EGCG on BAFF and PI3K/Akt/mTOR signaling, and then the apoptosis of B lymphocytes was promoted further.
为了研究 B 细胞激活因子（BAFF）属于 TNF 家族成员通过 PI3K/Akt/mTOR 信号通路在胶原诱导关节炎（CIA）大鼠 B 淋巴细胞抗凋亡中的作用，以及表没食子儿茶素没食子酸酯（EGCG）的调节作用。用 Sprague-Dawley 大鼠进行免疫诱导 CIA。CIA 大鼠随机分为不同组，用 EGCG（40、80mg/kg）、白芍苷（100mg/kg）从免疫后 18 天至 38 天治疗。通过 BAFF、抗 CII 抗体、IgA、IgG 和 IgM 的水平以及 BAFF 受体、P110δ、p-Akt、mTORC1、Bcl-xL 和 Bim 的表达来评估 EGCG 对 B 淋巴细胞的影响。通过 MTT 测定分析 B 淋巴细胞增殖。通过流式细胞术测定 B 淋巴细胞凋亡。结果表明，在 CIA 大鼠中，BAFF、抗 CII 抗体、IgA、IgG 和 IgM 水平升高。BAFF 受体、P110δ、p-AKT、mTORC1 和 Bcl-xL 表达高，而 Bim 表达降低。EGCG（40、80mg/kg）和白芍苷降低 CIA 大鼠中 BAFF、抗 CII 抗体、IgA、IgG、IgM 水平及 BAFF 受体、P110δ、p-AKT、mTORC1、Bcl-xL 的表达，并增加 Bim 表达。进一步的研究表明，EGCG 可以降低体外 P110δ和 mTORC1 的表达。EGCG 抑制 B 淋巴细胞增殖并诱导 B 淋巴细胞凋亡。综上所述，BAFF/BAFF 受体可能通过 PI3K/Akt/mTOR 通路调节 B 细胞抗凋亡。EGCG 对 CIA 大鼠有治疗作用，这可能与 EGCG 对 BAFF 和 PI3K/Akt/mTOR 信号的抑制作用有关，进而促进 B 淋巴细胞的凋亡。
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