调节性T细胞及其相关细胞因子转化生长因子β1白细胞介素10在儿童激素敏感型原发性肾病综合征发病机制中的作用

Effects of Treg cells and related cytokines TGF-β1 and IL-10 in pathogenesis of steroid-sensitive primary nephrotic syndrome in children

目的研究外周血调节性T细胞水平及其分泌的转化生长因子(TGF)-β1和白细胞介素-10(IL-10)在儿童激素敏感型原发性肾病综合征(SSNS)发病机制中的作用。方法选取2015年10月至2017年12月在山西省儿童医院肾内科确诊为原发性肾病综合征(PNS)初次住院治疗并经泼尼松足量治疗4周,尿蛋白阴转的患儿60例作为研究对象,分为泼尼松治疗前和治疗后2组。同期选定30名身体健康的儿童作为对照组,采用流式细胞术检测健康对照组和SSNS组泼尼松治疗前、后患者外周血Treg细胞比例,酶联免疫吸附试验(ELISA)法检测各组TGF-β1及IL-10水平。结果 SSNS患者Treg细胞比例为(6.55±1.74)%,较健康对照组(8.30±1.57)%)明显降低,经泼尼松治疗后Treg细胞比例为(8.16±1.67)%,较治疗前明显升高;SSNS患儿泼尼松治疗前血清TGF-β1水平明显高于对照组(P<0.01),治疗后TGF-β1水平较治疗前明显降低,差异有统计学意义(P<0.01),但与对照组比较差异无统计学意义(P>0.05);SSNS组患儿泼尼松治疗前血清IL-10水平明显低于对照组(P<0.05),治疗后较治疗前显著增高,且明显高于对照组,差异均有统计学意义(P<0.05)。结论 Treg细胞及其分泌的细胞因子TGF-β1及IL-10可能参与了儿童SSNS的发生及发展,明确Treg细胞及TGF-β1、IL-10在SSNS发病中的作用,可能为SSNS的治疗提供新的靶点和途径。

Objective To determine the effects of peripheral blood Treg cell levels and the secreted transforming growth factor(TGF-β1) and interleukin-10(IL-10) in the pathogenesis of steroid-sensitive primary nephrotic syndrome(SSNS) in children. Methods Sixty children with negative conversion of urinary protein, who were hospitalized in the Department of Nephrology, Shanxi Provincial Children's Hospital preliminarily and diagnosed with primary nephrotic syndrome(PNS) between October 2015 and December 2017, were included as the subjects in the study. All patients were treated with full-dose Prednisone, and were divided into pre-treatment and post-treatment groups. A contemporary cohort of 30 healthy children was included into the control group. The proportion of Treg cells in peripheral blood of normal control group and SSNS group at the baseline and after Prednisone treatment was deter-mined by flow cytometry. The levels of TGF-β1 and IL-10 in each group were measured by ELISA. Results The Treg cell proportion in SSNS group significantly decreased compared with that in the normal control group [(6.55 ±1.74)%vs.(8.30±1.57)%]. After the treatment with Prednisone, the Treg cell proportion in the SSNS group was(8.16 ±1.67)%,which significantly increased compared with that at the baseline. The serum level of TGF-β1 in SSNS group was significantly higher than that in the control group at the baseline(P<0.01). The serum level of TGF-β1 decreased significantly in SSNS group after the treatment with Prednisone compared with that at the baseline, with statistically signifi-cant difference(P< 0.01), whereas there was no statistically significant difference compared with that in the control group(P>0.05). The serum IL-10 level in SSNS group was significantly lower than that in the control group at the baseline(P<0.05). The serum IL-10 level in SSNS group significantly increased after the treatment with Prednisone compared with that at the baseline(P<0.05), and it was significantly higher than that in the control group, with statistically significant difference(P<0.05). Conclusion Treg cells and their secreted cytokines TGF-β1 and IL-10 may be involved in the occurrence and development of SSNS in children. To clarify the effects of Treg cells and TGF-β1 and IL-10 in the pathogenesis of SSNS may provide new targets and pathways for the treatment of SSNS.