Injurious effects of neutrophil extracellular trapping network on kidney of diabetic mice and its mechanisms
- VernacularTitle:中性粒细胞胞外诱捕网对糖尿病小鼠肾脏的损伤作用及其机制
- Author:
Wei-Hao CHEN
1
;
Xiao-Jun REN
;
Xin-Yue CHANG
;
Guan-Rui LI
;
Yan-Hong WANG
Author Information
- Keywords: neutrophil extracellular trap network; dia-betic kidney disease; pyroptosis; NF-κB; NLRP3 in-flammatory vesicles; kidney injury
- From: Chinese Pharmacological Bulletin 2024;40(12):2262-2269
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the promotional effects of neutrophil extracellular traps(NETs)on renal tissue damage and intestinal flora disruption induced by dia-betic kidney disease(DKD)and the potential mecha-nisms.Methods C57BL/6 mice were divided into:control group(NC),DNase Ⅰ control group(DNase Ⅰ)diabetic nephropathy group(DKD),and DNase Ⅰ treated group(DKD+DNase Ⅰ).The pathological changes of mouse kidney were observed by PAS,MAS-SON,and HE staining.The expression and distribu-tion of the relevant proteins of NETs in renal tissue of the mice in each group were observed by immunohisto-chemistry.The expression and distribution of coke-death-related proteins in the kidney tissues of mice in each group were observed by immunohistochemistry.The protein expression of NETs-related indexes,focal death-related indexes and NF-κB signaling pathway-re-lated indexes in kidney tissue of mice in each group were detected by immunoblotting.Results The ex-pression of indicators related to NETs was elevated in the DKD group,and their expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01).Patho-logical staining results showed that the kidneys of DKD mice were structurally abnormal,and the structure was improved after degradation of NETs by DNase Ⅰ.The results of immunohistochemical staining and immunob-lotting showed that the expression of pyroptosis-related proteins in kidney tissues of mice in the DKD group was elevated compared with that in the control group(P＜0.01).NF-κB-related signaling pathway protein expression profile expression rose,and its expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01)Conclusions NETs are generated in diabetic nephropathy and promote the onset of renal focal death and activation of the NF-κB signaling pathway,thereby exacerbating diabetes-induced kidney injury.
