Toll 样受体炎症级联反应与 1 型糖尿病儿童和青少年糖尿病肾病的发生发展。

Toll-like receptor inflammatory cascade and the development of diabetic kidney disease in children and adolescents with type 1 diabetes.

机构信息

Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Brazil.

Department of Clinical and Toxicological Analysis, University of São Paulo, São Paulo, Brazil.

出版信息

J Paediatr Child Health. 2022 Jun;58(6):996-1000. doi: 10.1111/jpc.15884. Epub 2022 Jan 10.

DOI:10.1111/jpc.15884

PMID:35006634

Abstract

AIM

This study aimed to evaluate the association of toll-like receptor (TLR) inflammatory cascade with the development of diabetic kidney disease (DKD) in children and adolescents with type 1 diabetes (T1D).

METHODS

A total of 49 T1D patients and 49 normoglycaemic (NG) subjects aged 5-20 years old were recruited. TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 mRNA expressions were measured in peripheral blood mononuclear cells by reverse transcription-quantitative polymerase chain reaction. Fasting glucose, glycated haemoglobin, serum urea, serum creatinine and urinary albumin-to-creatinine ratio (ACR) were determined.

RESULTS

The mRNA expressions of TLR2, TLR4, MYD88 and NFKB were significantly increased in the T1D group compared with the NG group. The mRNA expression levels of MCP1/CCL2 and IL18 were higher in 21 T1D patients (42.9%) (average of MCP1/CCL2: 6.6-fold and IL18: 5.8-fold) than in NG patients. Furthermore, ACR was increased in the T1D group compared with the NG group.

CONCLUSION

The increased mRNA expression of TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 favours the development of an inflammatory process that may lead to a decline in renal function and consequently DKD in children and adolescents with T1D. This suggests that these genes are early mediators of onset DKD since the beginning of the lives of the paediatric T1D patients.

摘要

目的

本研究旨在评估 Toll 样受体（TLR）炎症级联反应与 1 型糖尿病（T1D）儿童和青少年糖尿病肾病（DKD）的发展之间的关系。

方法

共招募了 49 名 T1D 患者和 49 名血糖正常（NG）的 5-20 岁受试者。通过逆转录定量聚合酶链反应（qRT-PCR）测定外周血单个核细胞中 TLR2、TLR4、MYD88、NFKB、MCP1/CCL2 和 IL18 mRNA 的表达。测定空腹血糖、糖化血红蛋白、血清尿素、血清肌酐和尿白蛋白/肌酐比（ACR）。

结果

与 NG 组相比，T1D 组 TLR2、TLR4、MYD88 和 NFKB 的 mRNA 表达显著增加。21 名 T1D 患者（42.9%）的 MCP1/CCL2 和 IL18 mRNA 表达水平较高（平均 MCP1/CCL2：6.6 倍，IL18：5.8 倍），高于 NG 患者。此外，与 NG 组相比，T1D 组的 ACR 增加。