中药新药与临床药理2025，Vol.36Issue(6)：888-898,11.DOI:10.19378/j.issn.1003-9783.2025.06.006
益气活血固肾颗粒通过调节Nox4抑制炎症和氧化应激改善糖尿病肾病肾脏纤维化
Yiqi Huoxue Gushen Granules Ameliorates Renal Fibrosis in Diabetic Nephropathy by Regulating Nox4 to Inhibit Inflammation and Oxidative Stress
摘要
Abstract
Objective To investigate the therapeutic effects of Yiqi Huoxue Gushen Granules(YHGG)on diabetic nephropathy(DN)model mice and its mechanisms related to inhibiting inflammation and oxidative stress.Methods Forty male C57BL/6 mice were randomly divided into a normal group,a model group,a YHGG group(585 mg·kg-1),and a metformin group(100 mg·kg-1).A DN mouse model was established by feeding a high-fat diet combined with intraperitoneal injection of Streptozotocin(STZ).After successful modeling,the mice were administered the corresponding doses once daily for 10 weeks.Body mass,blood glucose,lipid metabolism levels,organ indices,serum creatinine,blood urea nitrogen(BUN),and proteinuria were measured.Renal pathological changes were observed using Masson,PAS,and HE staining.Serum levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were measured by ELISA.Oxidative stress indicators,including catalase(CAT),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH),were determined using assay kits.RT-PCR and Western Blot were used to detect the mRNA and protein expression of fibrosis markers(α-SMA,TGF-β2,E-cadherin),inflammatory pathway markers(NLRP3,IL-1β,Caspase-1),oxidative stress pathway markers(Keap1,Nrf2),and the inflammation and oxidative stress-related target NADPH oxidase 4(Nox4)in renal tissues.Results Compared with the normal group,the model group showed significantly increased body mass,blood glucose,liver index,kidney index,BUN,urinary albumin excretion(UAE),serum creatinine(Scr),albumin-to-creatinine ratio(ACR),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),MDA,IL-1β,IL-6,and TNF-α levels(P＜0.01),and significantly decreased spleen index,urinary creatinine(Ucr),high-density lipoprotein cholesterol(HDL-C),CAT,SOD,and GSH levels(P＜0.01).The mRNA and protein expressions of α-SMA,TGF-β2,NLRP3,Caspase-1,IL-1β,Keap1,and Nox4 in renal tissues was significantly increased(P＜0.01,P＜0.001),while the mRNA and protein expression of E-cadherin and Nrf2 was significantly decreased(P＜0.05,P＜0.001).Compared with the model group,the YHGG group and metformin group showed significantly decreased body mass,blood glucose,liver index,kidney index,BUN,UAE,Scr,ACR,TG,TC,LDL-C,MDA,IL-1β,IL-6,and TNF-α levels(P＜0.05,P＜0.01,P＜0.001),and significantly increased spleen index,Ucr,HDL-C,CAT,SOD,and GSH levels(P＜0.05,P＜0.01,P＜0.001).The mRNA and protein expression of α-SMA,TGF-β2,NLRP3,Caspase-1,IL-1β,Keap1,and Nox4 in renal tissues was significantly decreased(P＜0.05,P＜0.01,P＜0.001),while the mRNA and protein expression of E-cadherin and Nrf2 was significantly increased(P＜0.05,P＜0.01,P＜0.001).Conclusion YHGG can inhibit inflammation and oxidative stress by regulating the Nox4-mediated NLRP3/Caspase-1 and Nrf2/Keap1 signaling pathways,thereby improving renal fibrosis and achieving therapeutic effects in diabetic nephropathy.关键词
益气活血固肾颗粒/糖尿病肾病/Nox4/炎症/氧化应激/肾脏纤维化/小鼠Key words
Yiqi Huoxue Gushen Granules/diabetic nephropathy/Nox4/inflammation/oxidative stress/renal fibrosis/mice分类
医药卫生引用本文复制引用
冯浩英华,房广庆,严玥,蒋希羽,全世建..益气活血固肾颗粒通过调节Nox4抑制炎症和氧化应激改善糖尿病肾病肾脏纤维化[J].中药新药与临床药理,2025,36(6):888-898,11.基金项目
广东省自然科学基金项目(2023A1515010843). （2023A1515010843）
