儿童原发性肾病综合征SOCS3表达与糖皮质激素耐药的相关性研究

doi:10.12372/jcp.2024.23e0597

摘要/Abstract

摘要：

目的研究原发性肾病综合征（PNS）患儿细胞因子信号转导抑制因子3（SOCS3）表达水平与糖皮质激素（GC）治疗反应性的关系。方法收集30例激素敏感型肾病综合征（SSNS）、16例激素耐药型肾病综合征（SRNS）患儿GC治疗前后及16例健康儿童外周静脉血，检测外周血单核细胞（PBMC）中SOCS3 mRNA以及血浆中SOCS3蛋白表达水平。同时检测PNS患儿GC治疗前后24小时尿蛋白定量（UTP）、血清肌酐（SCr）、血尿素氮（BUN）及肾小球滤过率（GFR），分析其与SOCS3表达的相关性。结果 GC治疗前，SSNS组与SRNS组患儿SOCS3 mRNA、蛋白表达水平均高于对照组儿童（P<0.05）。GC治疗6周时SSNS组SOCS3 mRNA、蛋白水平较治疗前下降（P<0.05），SRNS组SOCS3 mRNA表达相比治疗前无明显改变（P>0.05），SOCS3蛋白水平较治疗前升高（P<0.05）。GC治疗前后，SRNS组SOCS3 mRNA、蛋白表达水平均显著高于SSNS组（P<0.05）。PNS患儿SOCS3蛋白表达与24hUTP、SCr、BUN正相关（P<0.05），与GFR负相关（P<0.05）。结论 SRNS与SSNS患儿SOCS3表达水平存在差异，且差异与肾功能指标变化呈相关性，提示SOCS3表达上调对GC耐药的发生有潜在预测价值。

关键词: 细胞因子信号转导抑制因子3, 原发性肾病综合征, 糖皮质激素耐药

Abstract:

Objective To study the relationship between the expression of suppressor of cytokine signaling 3 (SOCS3) and the response to glucocorticoid(GC) treatment in children with primary nephrotic syndrome(PNS). Methods Peripheral venous blood samples were collected from 30 children with steroid-sensitive nephrotic syndrome (SSNS), 16 children with steroid-resistant nephrotic syndrome(SRNS) before and after GC treatment, and 16 healthy children. The expression of SOCS3 mRNA in peripheral blood monocytes (PBMC) and the expression of SOCS3 protein in plasma were detected. At the same time, the 24-hour urine protein, serum creatinine, blood urea nitrogen and glomerular filtration rate were measured before and after GC treatment in PNS children, and their correlation with SOCS3 expression was analyzed. Results Before GC treatment, the SSNS and SRNS groups had significantly higher mRNA and protein expression levels of SOCS3 than those of childen in the control group (P<0.05). After 6 weeks of GC treatment, the mRNA and protein levels of SOCS3 in SSNS group were lower than those before treatment (P<0.05), and the mRNA expression of SOCS3 in SRNS group showed no significant change compared with pre-treatment period (P>0.05), and the protein level of SOCS3 was increased compared to pre-treatment (P<0.05).Before and after GC treatment, the expression levels of SOCS3 mRNA and protein in the SRNS group were significantly higher than those in the SSNS group (P<0.05).The expression of SOCS3 protein in children with PNS was positively correlated with 24hUTP, SCr and BUN (P<0.05), and negatively correlated with GFR (P<0.05). Conclusion There were differences in the expression of SOCS3 between children with SRNS and SSNS, and the differences were correlated with the changes of renal function indexes. These results suggest that the up-regulation of SOCS3 expression has a potential predictive value for GC resistance.

Key words: suppressor of cytokine signaling 3, primary nephrotic syndrome, glucocorticoid resistance

庄亚飞, 程巾, 吴琛, 关凤军. 儿童原发性肾病综合征SOCS3表达与糖皮质激素耐药的相关性研究[J]. 临床儿科杂志, 2024, 42(5): 414-418.

ZHUANG Yafei, CHENG Jin, WU Chen, GUAN Fengjun. Association between SOCS3 expression and glucocorticoid resistance in children with primary nephrotic syndrome[J]. Journal of Clinical Pediatrics, 2024, 42(5): 414-418.

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项目	GC治疗前		t值	P	GC治疗6周		t值	P
项目	SSNS组	SRNS组	t值	P	SSNS组	SRNS组	t值	P
24-UTP/mg·kg^-1·d^-1	199.0±35.6	234.9±38.2	3.18	0.003	22.1±8.3¹⁾	72.4±28.2¹⁾	9.12	<0.001
SCr/μmol·L^-1	31.2±5.6	42.6±13.0	4.20	0.003	26.3±5.7¹⁾	27.5±7.8¹⁾	0.33	0.744
BUN/mmol·L^-1	4.3±1.0	8.3±2.0	9.03	<0.001	4.3±1.3	6.2±2.4¹⁾	3.57	0.008
GFR/mL·min^-1	175.5±30.3	115.6±29.7	6.43	<0.001	200.0±43.9¹⁾	158.4±53.5¹⁾	2.84	0.007

组别	例数	SOCS3 mRNA		t值	P
组别	例数	GC治疗前	GC治疗6周	t值	P
对照组	16	1.2±0.5	－	－	－
SSNS组	30	2.5±1.2¹⁾	1.3±0.5	5.39	<0.001
SRNS组	16	4.3±1.8¹⁾²⁾	4.6±1.4	0.46	0.651
统计量		F=97.52	t=11.84
P		<0.001	<0.001

组别	例数	SOCS3蛋白（pg/ml）		t值	P
组别	例数	GC治疗前	GC治疗6周	t值	P
对照组	16	82.1±6.1	－	－	－
SSNS组	30	100.4±16.2¹⁾	86.7±15.7	3.34	0.001
SRNS组	16	207.8±63.4¹⁾²⁾	317.0±69.7	4.64	<0.001
统计量		F=67.61	t=17.44
P		<0.001	<0.001