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  

Injurious effects of neutrophil extracellular trapping network on kidney ofdiabetic mice and its mechanisms

作　　者：陈伟豪 任小军 常欣悦 李关蕊 王艳红 CHEN Wei-hao;REN Xiao-jun;CHANG Xin-yue;LI Guan-rui;WANG Yan-hong(Dept of Microbiology and Immunology,School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China;Dept of Nephrology,Baiqiu'en Hospital,Taiyuan 030032,China;Innovative Center for Basic Pharmaceutical Research on Chronic Kidney Disease,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院微生物与免疫学教研室,山西太原030001 [2]山西白求恩医院肾内科,山西太原030032 [3]教育部慢性肾脏病医药基础研究创新中心,山西医科大学,山西太原030001

出　　处：《中国药理学通报》2024年第12期2262-2269,共8页Chinese Pharmacological Bulletin

基　　金：山西省人社厅留学基金项目(No 20210016);山西省自然科学研究面上项目(No 202203021221188);山西省应用基础研究计划项目(No 202103021224358)。

摘　　要：目的 研究中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)对糖尿病肾病(diabetic kidney disease,DKD)引起的肾脏组织损伤和肠道菌群紊乱的促进作用和潜在机制。方法 C57BL/6小鼠分为:对照组(NC),DNase I对照组(DNase I),糖尿病肾病组(DKD),DNase I处理组(DKD+DNase I),通过PAS、MASSON和HE染色观察小鼠肾脏病理变化,免疫组织化学法观察各组小鼠肾脏组织中NETs的相关蛋白及焦亡相关蛋白的表达和分布情况。免疫印迹法检测各组小鼠肾脏组织NETs的相关指标、焦亡相关指标和NF-κB信号通路相关指标的蛋白表达情况。结果DKD组中的NETs的相关指标表达升高,在DNase I对NETs降解后其表达下降(P <0.01),病理染色结果显示,DKD小鼠肾脏结构异常,在DNase I对NETs降解后结构有所好转,免疫组织化学染色和免疫印迹法结果显示,DKD组小鼠肾脏组织的焦亡相关蛋白表达相较于对照组表达上升(P<0.01),在DNase I对NETs进行降解后其表达下降。NF-κB信号通路相关蛋白表达情况表达上升,在DNase I对NETs进行降解后其表达下降(P<0.01)。结论NETs在糖尿病肾病中生成,并促进肾脏焦亡的发生,激活NF-κB信号通路,从而加剧糖尿病导致的肾脏损伤。Aim To investigate the promotional effects of neutrophil extracellular traps(NETs)on renal tissue damage and intestinal flora disruption induced by diabetic kidney disease(DKD)and the potential mechanisms.Methods C57BL/6 mice were divided into:control group(NC),DNaseⅠcontrol group(DNaseⅠ)diabetic nephropathy group(DKD),and DNaseⅠtreated group(DKD+DNaseⅠ).The pathological changes of mouse kidney were observed by PAS,MASSON,and HE staining.The expression and distribution of the relevant proteins of NETs in renal tissue of the mice in each group were observed by immunohistochemistry.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-related indexes in kidney tissue of mice in each group were detected by immunoblotting.Results The expression 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).Pathological 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 immunoblotting 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.

关 键 词：中性粒细胞胞外诱捕网 糖尿病肾病 焦亡 NF-ΚB NLRP3炎症小体 肾脏损伤 

分 类 号：R-332[医药卫生] R322.61R331.123R364.5R587.1R692.39