三七皂苷对系统性红斑狼疮患者外周血淋巴细胞P-糖蛋白及激素效应的影响

The effects of Panax Notoginseng Saponins on P-glycoprotein and the function of glucocorticoid in lymphocytes of systemic lupus erythematosus patients

目的 探讨系统性红斑狼疮（SLE）患者糖皮质激素耐药机制以及三七皂苷逆转耐药的作用.方法 直线相关分析SLE患者外周血淋巴细胞P-糖蛋白与SLE疾病活动指数（SLEDAI）、临床疗效的相关性.用三七皂苷干预患者外周血淋巴细胞,维拉帕米为对照,流式细胞术检测淋巴细胞P-糖蛋白、罗丹明123以及联合甲泼尼龙干预的细胞凋亡率.采用方差分析或t检验进行统计学分析.结果 SLE患者外周血淋巴细胞P-糖蛋白与SLEDAI呈正相关（r=0.490,P〈0.05）,缓解组P-糖蛋白（12.2±2.5）%与部分缓解或无效组（16.5±4.0）%差异有统计学意义.三七皂苷干预组P-糖蛋白（11.2±3.1）%和罗丹明123（70.1±5.8）%与对照组[分别为（15.3±2.9）%,（53.9±5.2）%]比较差异有统计学意义.三七皂苷可协同甲泼尼龙诱导淋巴细胞凋亡.结论 三七皂苷下调P-糖蛋白表达和转运活性的双重作用可能是协同甲泼尼龙诱导淋巴细胞凋亡的重要机制.

Objective To investigate the mechanism of glucocorticoid resistance in patients with systemic lupus erythematosus（SLE） and the effects of Panax Notoginseng Saponins（PNS） on reversing glucocorticoid resistance in lymphocytes. Methods The relevance between P-glycoprotein （P-gp, %） and SLEDAI integrals or clinical effects was analyzed by linear correlation analysis. The lymphocytes from SLE patients were intervened with PNS or verapamil. P-gp of the lymphocytes and Rhodamine 123 （Rh123, %） accumulated in the lymphocytes were assayed by flow cytometry. The percentage of the apoptosis of the lymphocytes stimulated with PNS or verapamil combined with methylprednisolone was identified by double-tagging with Annexin V and propidium iodide （PI） and detected by flow cytometry. Variance analysis or Student＇s t test was used for statistics. Results The P-gp in the peripheral blood lymphocytes of SLE patients was significantly related to SLEDAI integrals. The difference of P-gp between lymphocytes in the completely remission cases （12.2±2.5）% and lymphocytes in the partial remission or non-effective cases （16.5±4.0）% was statistically significantce. The difference of P-gp and Rh123 between lymphocytes treated with PNS [（11.2±3.1）%,（70.1 ±5.8）% respectively ] and lymphocytes of the control group [ （15.3±2.9）%, （53.9±5.2）% respectively ]was statistically significant. The lymphocytes apoptosis rate in the lymphocytes stimulated with methylprednisone combined with PNS increased significantly compared to the lymphocytes stimulated with methylprednisolone only. Conclusion The action of PNS in suppressing both the expression and the transfer activity of P-gp is possibly the important mechanism to increase the effects of methylprednisolone in inducing lymphocytes apoptosis.