中医临床研究2025,Vol.17Issue(11):63-71,9.DOI:10.3969/j.issn.1674-7860.2025.11.011
基于核苷酸结合低聚域样受体蛋白3/半胱氨酸蛋白酶1信号通路探讨芪黄方改善糖尿病肾脏疾病db/db小鼠蛋白尿的作用机制
Exploring the mechanism of the Qihuang prescription in improving proteinuria in diabetic nephropathy db/db mice based on the NLRP3/CASP1 signaling pathway
摘要
Abstract
Objective:To observe the effects of the Qihuang prescription(芪黄方)on the NLRP3/CASP1 signaling pathway and proteinuria in diabetic nephropathy db/db mice.Methods:Fifty db/db mice were randomly divided into the model group,the Qihuang prescription high dose group,the Qihuang prescription middle dose group,the Qihuang prescription low dose group,and the losartan potassium group,with 10 mice in each group.Additionally,10 db/m mice were selected as the normal group.After 12 weeks of continuous administration,the general conditions of the mice were observed.Glucose,24-hour urine protein quantification,and urinary albumin/creatinine ratio(ACR)were measured at week 0 and week 12 of administration.After 12 weeks of administration,samples were collected,and serum creatinine(Scr),blood urea nitrogen(BUN),total cholesterol(TC),triglycerides(TG),and low density lipoprotein cholesterol(LDL-C)indicators were measured.Renal histopathological morphology was observed using HE staining.The protein contents of NLRP3,CASP1,and IL-18 in the serum of mice were detected using ELISA.Results:Compared with the normal group,the body mass,blood glucose,24-hour urine protein quantitation,ACR,Scr,and BUN levels in the db/db mice in the model group were significantly increased(P<0.01).The expression of serum inflammatory factors such as IL-1,IL-18,and TGF-β1 was upregulated(P<0.01).The protein levels of NLRP3 and CASP1 in the kidney tissues of mice were increased,with no statistical difference between db/db mice groups(P>0.05).After 9-12 weeks of administration,the general state in the Qihuang prescription high dose group and middle dose group was significantly ameliorated,with a decreasing trend in body weight,showing statistical differences compared with the model group(P<0.05 or P<0.01).Blood glucose,24-hour urine protein quantitation,and ACR levels in different dose groups of the Qihuang prescription and the losartan potassium groups were significantly decreased(P<0.05 or P<0.01).Scr and BUN levels were significantly decreased(P<0.05).TC,TG,and LDL-C levels were decreased(P<0.05).The expressions of serum inflammatory factors such as IL-1,IL-18,and TGF-β1 were significantly decreased(P<0.05 or P<0.01).The protein contents of NLRP3 and CASP1 in kidney tissues were significantly decreased.HE staining under light microscopy showed reduced inflammatory cell infiltration and ameliorated pathological damage in kidney tissues.Conclusion:The Qihuang prescription may reduce renal inflammatory response and protect podocytes by inhibiting the NLRP3/CASP1 signaling pathway,thereby achieving the effect of reducing proteinuria excretion in diabetic nephropathy.关键词
糖尿病肾脏疾病/芪黄方/db/db小鼠/核苷酸结合低聚域样受体蛋白3/半胱氨酸蛋白酶1信号通路/蛋白尿Key words
Diabetic nephropathy/The Qihuang prescription/db/db mice/NLRP3/CASP1 signaling pathway/Proteinuria分类
医药卫生引用本文复制引用
刘春光,朱庆爽,赵悦,王君红,陈晨,雷蕾,苑天彤,迟继铭..基于核苷酸结合低聚域样受体蛋白3/半胱氨酸蛋白酶1信号通路探讨芪黄方改善糖尿病肾脏疾病db/db小鼠蛋白尿的作用机制[J].中医临床研究,2025,17(11):63-71,9.基金项目
黑龙江省自然科学基金课题(LH2022H057):基于"脾为之卫"探讨芪黄方通过调控Nrf2/HO-1/NLRP3信号通路改善db/db小鼠蛋白尿的机制. (LH2022H057)