外周血转化生长因子-β_1白介素-18mRNA表达与儿童原发性肾病综合征激素耐药关系探讨

Relationship between the expression levels of TGF-β1and IL-18 mRNA and hormone resistance in children with primary nephrotic syndrome

目的探讨检测外周血转化生长因子（TGF）-β1和白介素（IL）-18 mRNA表达水平对于儿童原发性肾病综合征（PNS）激素耐药的临床意义。方法对2012年11月至2013年10月天津市儿童医院PNS组患儿分别在激素治疗前、治疗1周、治疗4周取血,纳入正常对照组儿童取血。通过RT-PCR检测外周血单个核细胞（PBMC）中TGF-β1和IL-18mRNA的表达水平。结果在激素治疗前、1周、4周时,激素敏感型肾病综合征（SRNS）组TGF-β1和IL-18 m RNA的水平均高于激素耐药型肾病综合征（SSNS）组（P〈0.05）。正规激素治疗1周、4周后,SSNS组TGF-β1和IL-18 mRNA的水平随时间均逐渐下降（P〈0.05）。SRNS组经正规激素治疗1周时,TGF-β1mRNA的水平比激素治疗前降低（P〈0.05）。与治疗1周时比较,SRNS组治疗4周时,IL-18 m RNA降低（P〈0.05）。受试者工作特征曲线（ROC）分析,PBMC中TGF-β1、IL-18 m RNA在诊断SRNS的ROC曲线下面积0.89和0.68。诊断临界点分别为0.44和0.13,其对应灵敏度分别为82.6%和65.2%,特异度分别为83.3%和72.2%。结论在儿童PNS开始激素治疗的1~4周,PBMC中TGF-β1、IL-18 mRNA的表达水平持续增高,提示PNS患儿有发生激素耐药的风险。在激素应用前,当PBMC中TGF-β1mRNA的表达量≥0.44时应警惕PNS患儿出现激素耐药。

Objective To investigate the clinical significance of the mRNA expression level of IL- 18 and TGF- β1 in children with primary nephrotic syndrome （PNS）. Methods Blood is collected from children with PNS group before glucoeorticoids （GC） treatment （0 weeks）, 1 week and 4 weeks after treatment and the control group. The mRNA levels of IL-18 and TGF-β1 were measured by RT-PCR, while the biochemical factor levels of Cr, BUN, β2-MG, CysC, TP, Alb, Tcho and 24 h UP were tested. Results The mRNA levels of TGF-β1 and IL-18 were significantly higher in SRNS group than SSNS group before GC treatment and at 1 and 4 weeks after treatment （P 〈 0.05） ;the levels of other biochem- ical factors had no significant difference （P 〉 0.05）. At 1 and 4 weeks after GC threatment, the mRNA levels of TGF-β1 and IL-18 gradually decreased with time in SSNS group （P 〈 0.05）. At 1 week after GC threatment, the mRNA level of IL-18 wasn＇t lower than before GC threatment （P 〉 0.05） ; the mRNA level of TGF-β1 was significantly lower than be- fore GC treatment （P 〈 0.05）. At 4 weeks after GC threatment, the mRNA level of IL- 18 was lower than 1 week （P 〈 0.05）, while the mRNA level of TGF-β1 wasn＇t lower （P 〉 0.05）. The area under the ROC curve of TGF-[3~ and IL-18 were 0.89 and 0.68 respectively. The optimal operating point were 0.44 and 0.13 respectively, the sensitivity 82.6% and 65.2% respectively, specificity 83.3%and 72.2%respectively. Conclusion In 1 - 4 weeks of GC treatment,if the levels of TGF-β1 and IL-18 mRNA expression in PBMC do not decrease significantly, the risk of SRNS is high. The mRNA ex-pression level of TGF-β1 ≥0.44 can be used as a quantita- tive index to predict SRNS.