表没食子儿茶素没食子酸酯通过调节BAFF介导的凋亡蛋白失衡发挥对CIA大鼠的治疗作用

摘要

目的 研究大鼠胶原性关节炎(Collagen induced arthritis,CIA)B淋巴细胞BAFF介导的凋亡蛋白表达失衡及EGCG的调节作用.方法 建立SD大鼠CIA模型,将其随机分组,免疫后18～38 d分别给予EGCG(40,80 mg·kg-1)和Pae(100 mg·kg-1)处理,测定血清中BAFF、抗Ⅱ型胶原抗体、IgA、IgG和IgM的水平及抗凋亡蛋白Bcl-xL和促凋亡蛋白Bim的表达.结果 CIA大鼠足爪肿胀,关节炎指数升高,血清BAFF、抗Ⅱ型胶原抗体、IgA、IgG、IgM水平上调,Bcl-xL表达增加,而Bim表达减少.EGCG(40,80 mg·kg-1)和Pae(100 mg·kg-1)能明显降低CIA大鼠关节炎指数,足爪肿胀度,降低CIA大鼠中升高的BAFF、抗Ⅱ型胶原抗体、IgA、IgG、IgM水平,并降低Bcl-xL的表达,而上调下降的Bim表达.结论 BAFF通过促进Bcl-xL表达,抑制Bim表达而参与B细胞抗凋亡过程,EGCG调节BAFF介导的凋亡蛋白失衡是其发挥对CIA大鼠治疗作用的机制之一.%Objective To investigate the unbalance of apoptotic protein mediated by BAFF in B lymphocytes in rats with collagen-induced arthritis (CIA) and the regulation of EGCC. Methods SD rats were immunized to induce CIA. CIA rats were randomly divided into several groups and treated with EGCG at the concentration of 40 and 80 mg ·kg-1 and Pae at the 100 mg · kg-1 respectively from day 18 to day 38 after immunization. The effects of EGCG on B lymphocytes of CIA rats were evaluated by the levels of BAFF, anti-CH antibody, IgA, IgC and IgM, and the expressions of Bcl-xL and Bim. Results The secondary inflammatory response and paw swelling were observed in CIA rats, and arthritis scores were high. The levels of BAFF, anti-CII antibody, IgA, IgG and IgM in serum were enhanced. The expression of anti-apoptotic protein Bcl-xL was increased greatly, while the pro- apoptotic protein Bim was decreased. EGCG (40, 80 mg · kg-1 ) and Pae (100 mg · kg-1 ) obviously decreased arthritis score and paw swelling in CIA rats. EGCG (40,80 mg · kg-1) and Pae (100 mg · kg-1 ) decreased the levels of BAFF, anti-CII antibody, IgA, IgG and IgM. EGCG (40, 80 mg · kg-1) and Pae (100 mg · kg-1) also significantly decreased the expressions of Bcl-xL, and increased the expression of Bim in CIA rats. Conclusion BAFF participated in anti- apoptosis progress through promoting Bcl-xL expression and inhibiting Bim expression. One of the mechanisms of therapeutic effects of EGCG is to regulate the unbalance of apoptotic protein mediated by BAFF.