地塞米松对儿童原发性系膜增生性肾炎外周血淋巴细胞CTLA-4表达和凋亡的影响

Effects of dexamethasone on CTLA-4 expression and apoptosis in lymphocytes obtained from children with mesangial proliferative nephritis

摘要:

目的：原发性系膜增生性肾炎(MsPGN)的发病机制和糖皮质激素(GC)耐药机制虽然部分已明确，但其确切机制仍未阐明。细胞毒性T淋巴细胞相关抗原(CTLA-4)是T细胞活化的重要抑制性分子。本研究探讨MsPGN患儿外周血淋巴细胞CTLA-4表达和淋巴细胞凋亡及地塞米松(Dex)对其影响。方法：分别采用直接免疫荧光、流式细胞仪及Annexin V-FITC/PI双染流式细胞仪检测Dex处理或非Dex处理的MsPGN组和对照组体外培养外周血淋巴细胞膜CTLA-4的表达和其凋亡。结果：体外培养MsPGN组淋巴细胞CTLA-4的自然表达和Dex诱导的表达均较对照组低（P＜0.05）；MsPGN组淋巴细胞自然凋亡和Dex诱导的凋亡亦较对照组低（P＜0.05），且两者均呈正相关性（P＜0.05）。结论：CTLA-4表达异常可能参与了MsPGN的发病机制及GC耐药机制。［中国当代儿科杂志，2009，11（12）：957-960］

Abstract:

OBJECTIVE: The pathogenesis of mesangial proliferative glomerulonephritis (MsPGN) and mechanisms of glucocorticoid (GC) resistance have not been fully identified. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte activation. The objective of the study is to investigate the CTLA-4 expression and apoptosis in lymphocytes of children with MsPGN and the effects of dexamethasone (Dex) on the CTLA-4 expression and apoptosis. METHODS: Blood samples were collected from 36 children with MsPGN and 30 healthy children. CTLA-4 expression in in vitro cultured lymphocytes with or without Dex treatment was measured by flow cytometry following direct immune fluorescene. The rate of apoptosis in the lymphocytes was evaluated by annexin V-FITC and propidium iodide staining. RESULTS: The CTLA-4 expression and apoptosis in lymphocytes from children with MsPGN were significantly lower than those in the healthy control children in the absence or presence of Dex treatment (P＜0.05). There was a positive correlation between CTLA-4 expression and apoptosis in lymphocytes (P＜0.05). CONCLUSIONS: Abnormal CTLA-4 expression may participate in the pathogenesis of MsPGN and be one of mechanisms of GC resistance.［Chin J Contemp Pediatr, 2009, 11 (12):957-960］