青藤碱治疗类风湿性关节炎免疫作用和机制

Immunopharmacological action of sinomenine, an alkaloid isolated from Sinomenium acutum, and its mechanism of action in treating rheumatoid arthritis

目的 研究青藤碱(sinomenine,SIN)对动物免疫功能和细胞凋亡的影响及对人滑膜细胞增殖影响。方法MTT法测定脾淋巴细胞增殖反应及滑膜细胞增殖反应。采用流式细胞术测定脾T淋巴细胞亚型。流式细胞仪和DNALadder测定脾淋巴细胞凋亡。结果 SIN在体给药抑制LPS及PMA诱导的小鼠脾淋巴细胞增殖。SIN离体给药可抑制ConA,LPS和anti CD3mAb诱导小鼠脾淋巴细胞增殖;SIN可使AA大鼠升高的CD4+ /CD8+比值降低。SIN体外使小鼠脾淋巴细胞早期凋亡百分比显著增加。SIN对人类风湿关节炎滑膜细胞增殖也有抑制作用。结论SIN对小鼠和类风湿关节炎大鼠脾淋巴细胞免疫功能具有抑制作用,诱导细胞凋亡可能是SIN免疫抑制作用的机理之一。

Aim To observe the effects of sinomenine on the immune functions and apoptosis of murine lymphocyte as well as on human synovial fibroblast proliferation. Methods Both in vivo and in vitro tests were adopted. The lymphocyte proliferation induced by mitogens was assayed by MTT method. Spleen T lymphocyte subtypes were tested with flow cytometry. Spleen lymphocyte apoptosis was analyzed by flow cytometry and DNA ladder methods. In vitro test was adopted to observe the effects of sinomenine on the proliferation of human fibroblast of rheumatoid arthritis. Results Sinomenine can inhibit the proliferation of mouse lymphocytes induced by ConA, LPS and anti-CD3 mAb but not PMA in vitro, and inhibit the proliferation induced by LPS and PMA in vivo. Sinomenine can reduce up-regulated CD4+/CD8+ ratio of T lymphocyte subtype in adjuvant arthritis rat. At the same concentration increased apoptosis ratio. As to human synovial fibroblast, sinomenine can significantly inhibit proliferation of human fibroblast. Conclusion Sinomenine can inhibit the immunological function and correct imbalance of CD4+/CD8+ ratio of T lymphocyte subtype. It can also increase apoptosis ratio of spleen lymphocyte. This may be the mechanism of its immunological inhibitory effect.