原花青素对佐剂关节炎大鼠滑膜细胞Bcl-2、Bax表达的影响

Effects of proanthocyanidins on the expression of Bcl-2 and Bax in synoviocytes of adjuvant arthritis rats

目的:研究原花青素(PC)对佐剂关节炎大鼠滑膜细胞Bc1-2、Bax表达的影响。方法:采用大鼠佐剂性关节炎(AA)模型,逆转录聚合酶链反应(RT-PCR)测定各组大鼠滑膜细胞Bcl-2、BaxmRNA的水平,免疫印迹法(Westernblotting)检测各组大鼠滑膜细胞Bcl-2、Bax蛋白表达,分析滑膜细胞caspase-3酶原的裂解,比色法测定大鼠滑膜细胞caspase-3的相对活性。结果:正常大鼠滑膜细胞Bcl-2和Bax均有表达,模型组大鼠Bcl-2、Bax表达均高于正常组。PC(6,30mg/kg)治疗组可明显下调Bcl-2mRNA和蛋白的表达,上调BaxmRNA和蛋白表达;而caspase-3酶原的表达随药物浓度的增加而减少,药物组大鼠caspase-3与对照组相比活性升高。结论:PC可通过下调滑膜组织中Bcl-2表达、上调Bax表达,诱导caspase-3活化,从而诱导滑膜细胞凋亡,这可能是其治疗佐剂性关节抗炎的机制之一。

Aim： To investigate the effects of proanthoeyanidins on the expression of Bcl-2 and Bax in synovium of adjuvant arthritis rats. Methods：In the adjuvant arthritis-induced rat model, the expressions of Bcl-2 and Bax mRNA in the synoviocytes in the control and adjuvant arthritis-induced groups were analyzed by RT-PCR. The protein expre ssions of Bcl-2 and Bax in the synoviocytes as well as the cleavages of pro-caspase-3 were further analyzed by Western blotting. In addition, the relative activities of caspase-3 were determined by colorimetry. Results： The mRNA and protein expressions of Bcl-2 and Bax were higher in the synovioeytes of adjuvant arthritis-induced rat than those in normal control. Treatment using proanthoeyanidins （6 mg/kg and 30 mg/kg） resulted in the considerable down-regulation of the expression of Bcl-2 in the synoviocytes of adjuvant arthritis-induced rats but the significant up-regulation of the expression of Bax. The expression of pro-caspase-3 decreased as increases in proanthoeyanidins concentration. The activity of caspase-3 in the treatment group was higher than that in the control, and the changes in the concentration-depen- dent manner existed. Conclusion： Proanthoeyanidins might promote the apoptosis of synovioeytes via the decreased expression of Bcl-2, the up-regulated expression of Bax and the induced activation of caspase-3. These findings might be attributable to the anti-inflammatory mechanisms of proanthocyanidins to adjuvant arthritis.