肿瘤坏死因子-α及其单克隆抗体抗对肾病综合征复发激素治疗的影响

The influence of tumor necrosis factor and its monoclonal antibody on hormone therapy in patients with recurrence of nephrotic syndrome

目的研究肿瘤坏死因子(TNF-α)及其单克隆抗体(单抗)对肾病综合征(NS)复发患者糖皮质激素受体(GR)表达的影响。方法用酶联免疫吸附测定(ELISA)、实时定量荧光PCRReal time PCR)方法检测不同浓度、不同时间TNF-α和不同浓度TNF-α单抗刺激后正常人和NS复发患者培养液上清中GR、外周血单个核细胞(PBMC)中GR m RNA的表达。结果 1以200 pg/m L的TNF-α刺激培养PBMC后GR表达高于对照组(P<0.05),以500 pg/m L的TNF-α刺激培养PBMC后GR表达低于对照组(P<0.05);2TNF-α刺激PBMC 12及24 h后GR表达均高于对照组(P<0.05),24 h时的变化更明显(P<0.01);3以2 000及20 000 pg/m L的TNF-α单抗刺激PBMC后GR表达均低于对照组(P<0.05),2000 pg/m L组的变化更明显(P<0.01)。结论 TNF-α可影响NS复发患者GR的表达,且与时间及剂量相关,TNF-α单抗可以缓解TNF-α所引起的GR的改变,且与剂量相关。

【Objective】 To study the effect of tumor necrosis factor and its monoclonal antibody on glucocorticoid receptor expression in patients with nephrotic syndrome.【Methods】The different concentrations of TNF-α and TNF-α monoclonal antibody at different times were used to stimulate PBMC in normal subjects and patients with relapsed NS, ELISA was used to detect the expression of supernatant GR in the culture supernatant and GRm RNA in PBMC.【Results】1After stimulation of TNF-α with concentrations of 200pg/m L,the expression of GR was higher than control（P〈0.05）, with 500pg/m L, the expression was lower than the control group（P〈0.05）; 2After the stimulation of TNF-a for 12 h, 24 h, the expression of GR was higher than the control group（P〈0.05）, the change was more obvious at 24h（P〈0.01）; 3After stimulation of TNF-α monoclonal antibody with concentrations of 2000pg/m L and 20 000pg/m L, the expression of GR was lower than control（P〈0.05）, the change was more obvious after stimulation of 2 000 pg/m L（P〈0.01）. 【Conclusions】TNF-α can affect the expression of GR in patients with recurrent nephrotic syndrome,which is associated with time and dose, TNF-α monoclonal antibody can ease the change caused by TNF-α, and is associated with dose.