中国中医药信息杂志2025，Vol.32Issue(6)：112-120,9.DOI:10.19879/j.cnki.1005-5304.202406119
通络保肾方调控Gprc5b/NF-κB/NLRP3通路改善IgA肾病大鼠足细胞损伤的机制研究
Study on the Mechanism of Tongluo Baoshen Decoction in Regulating Gprc5b/NF-κB/NLRP3 Pathway to Improve Podocyte Injury in IgA Nephropathy Rats
摘要
Abstract
Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.关键词
通络保肾方/IgA肾病/足细胞/Gprc5b/NF-κB/NLRP3通路/大鼠Key words
Tongluo Baoshen Decoction/IgA nephropathy/podocyte/Gprc5b/NF-κB/NLRP3 pathway/rats分类
医药卫生引用本文复制引用
刘永芳,傅奕,周莉,刘晖扬,代建风,刘英华,陈帮明,林雪菲,杨太旺,刘星宇..通络保肾方调控Gprc5b/NF-κB/NLRP3通路改善IgA肾病大鼠足细胞损伤的机制研究[J].中国中医药信息杂志,2025,32(6):112-120,9.基金项目
国家自然科学基金(82060839) （82060839）
江西省中医肾病临床医学研究中心建设项目(2019BCD42006) （2019BCD42006）
国家中医优势专科(肾病科)建设项目(2023年) （肾病科）
江西省中医优势病种肾衰病防治中心建设项目(2021年) （2021年）
全国名老中医药专家传承工作室建设项目(2022年) （2022年）
