中药新药与临床药理2026，Vol.37Issue(4)：686-693,8.DOI:10.19378/j.issn.1003-9783.2026.04.011
基于Nrf2信号通路探讨活络效灵丹对糖尿病大鼠肾损伤的保护作用及机制
Investigating the Protective Effect and Mechanism of Huoluo Xiaoling Dan on Renal Injury in Diabetic Rats Based on the Nrf2 Signaling Pathway
摘要
Abstract
Objective To explore the protective effect and mechanism of Huoluo Xiaoling Dan on renal injury in diabetic rats based on the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Methods SD rats were randomly divided into the normal group,model group,Cozaar group(10 mg·kg-1),and low-and high-dose Huoluo Xiaoling Dan groups(5.4,10.8 g·kg-1),with 6 rats in each group.A diabetic rat model was induced by high-sugar and high-fat diet feeding combined with a single intraperitoneal injection of a low dose of streptozotocin(35 mg·kg-1).Each treatment group received the corresponding dose by oral gavage once daily for 8 consecutive weeks.Body mass and fasting blood glucose(FBG)were measured at weeks 0,2,4,6,and 8 of drug intervention.An automatic biochemical analyzer was used to detect 24-hour urinary protein and urinary creatinine in urine,as well as serum levels of blood urea nitrogen(BUN),serum creatinine(Scr),total cholesterol(TC),and triglycerides(TG);creatinine clearance rate(CCr)was calculated.Renal histopathological changes were observed by HE staining.Biochemical methods were used to measure the levels of oxidative stress markers superoxide dismutase(SOD)and malondialdehyde(MDA)in serum and renal tissue.ELISA was used to detect serum insulin and Nrf2 levels,and the insulin resistance index(HOMA-IR)was calculated.Western Blot was performed to detect the protein expression levels of Nrf2,heme oxygenase-1(HO-1),and NAD(P)H quinone oxidoreductase 1(NQO1)in the renal cortex of rats.Results Compared with the normal group,the model group showed a significant decrease in body mass(P＜0.01);FBG levels were significantly increased(P＜0.01);serum TC levels and HOMA-IR were significantly increased(P＜0.01);kidney index,BUN,24-hour urinary protein,and CCr were all significantly elevated(P＜0.05,P＜0.01);MDA content in serum and renal tissue was significantly increased(P＜0.01),while serum SOD and Nrf2 levels were significantly decreased(P＜0.01);protein expression of Nrf2,HO-1,and NQO1 in the renal cortex was significantly downregulated(P＜0.01).Compared with the model group,body mass in the low-dose Huoluo Xiaoling Dan group was significantly increased at weeks 4 and 6 of intervention(P＜0.05),and in the high-dose group at weeks 6 and 8(P＜0.01);FBG levels in the high-dose group were significantly decreased at week 8(P＜0.05);serum TC levels and HOMA-IR were significantly reduced in both the low-and high-dose groups(P＜0.05,P＜0.01);kidney index was significantly decreased in the low-dose group(P＜0.01);BUN,24-hour urinary protein,and CCr were significantly decreased in both the low-and high-dose groups(P＜0.05,P＜0.01);MDA content in serum and renal tissue was significantly reduced(P＜0.05,P＜0.01),while serum SOD and Nrf2 levels were significantly increased(P＜0.05,P＜0.001);protein expression of Nrf2 and NQO1 in the renal cortex was significantly upregulated in both the low-and high-dose groups(P＜0.05,P＜0.01),and HO-1 protein expression was significantly upregulated in the low-dose group(P＜0.05).Conclusion Huoluo Xiaoling Dan has a certain ameliorative effect on renal lesions in diabetic rats,which may be related to regulating the Nrf2 signaling pathway and improving oxidative stress in the body.关键词
活络效灵丹/糖尿病/肾损伤/氧化应激/Nrf2 信号通路/大鼠Key words
Huoluo Xiaoling Dan/diabetes/renal damage/oxidative stress/Nrf2 signal pathway/rats分类
医药卫生引用本文复制引用
孙靖烨,余松远,谭晓,金周慧,王海颖..基于Nrf2信号通路探讨活络效灵丹对糖尿病大鼠肾损伤的保护作用及机制[J].中药新药与临床药理,2026,37(4):686-693,8.基金项目
上海市卫生健康委员会科研发展基金项目(202150030) （202150030）
浦东新区国家中医药改革示范区项目(YC-2023-0605) （YC-2023-0605）
浦东新区国家中医药传承创新发展试验区建设项目(PDZY-2025-0919). （PDZY-2025-0919）
