霉酚酸及地塞米松对系统性红斑狼疮患者外周血淋巴细胞凋亡的影响

目的:以地塞米松(DEX)为对照,观察新型免疫抑制剂霉酚酸(MPA)对系统性红斑狼疮(SLE)患者外周血淋巴细胞凋亡的作用。方法:分离12例SLE患者及8例健康对照的外周血单个核细胞(PBMCs),分别加或不加MPA/DEX培养48h,用ELISA法测培养上清中sFas与sFasL的水平,用AV鄄FITC/PI双标记流式细胞术测PBMCs的凋亡率。结果:SLE患者PBMCs培养上清中的sFasL水平较正常对照显著增高,而MPA及DEX均可使其分泌的sFas及sFasL水平显著下降,且MPA使sFasL降低的程度较sFas更显著,而DEX却正相反。SLE患者培养的PBMCs凋亡率较正常对照显著增高,MPA及DEX均可使凋亡率进一步增加,而DEX较MPA对凋亡的诱导作用更加显著。结论:MPA及DEX对SLE患者PBMCs具有促进凋亡的作用,但这一作用可能并非通过Fas鄄FasL途径;而且,在诱导凋亡方面,MPA与DEX的作用既有相同,又存在差异。

Effects of mycophenolic acid and dexamethasone on apoptosis of cultured PBMCs from patients with SLE

Objective:To investigate the effect of novel immunosuppressant mycophenolate acid(MPA), by comparison with dexamethasone(DEX), on apoptosis of cultured peripheral blood mononuclear cells(PBMCs) from patients with systemic lupus erythematosus. Methods: PBMCs were prepared from heparinized venous blood of SLE patients and healthy controls. After 48 hours of cell culture with or without addition of MPA/DEX,the levels of sFas and sFasL in the supernatants were measured by ELISA. Meanwhile, AV-FITC/PI two color flow cytometry was applied to detect the percentage of cells undergoing apoptosis. Results:While PBMCs from SLE patients showed a significant increase of apoptosis rate compared with normal controls, the levels of sFasL in the supernatants of cultured PBMCs from SLE were also significantly elevated. MPA and DEX could both significantly reduce the production of sFas and sFasL by and promote apoptosis of SLE PBMCs. While DEX inhibited the production of sFas by and induced apoptosis of SLE PBMCs to a higher extent, MPA reduced the production of sFasL more. Conclusion:Both MPA and DEX can enhance apoptosis of PBMCs from SLE patients. Though the apoptosis-inducing effect of the two agents shows both similarities and differences, it may not be mediated through Fas-FasL pathway.