解放军医学院学报2024，Vol.45Issue(3)：261-269,9.DOI:10.12435/j.issn.2095-5227.2023.119
山柰酚通过改善肾小管上皮细胞的氧化应激与炎症反应减轻1型糖尿病小鼠肾损伤
Kaempferol alleviates renal injury in type 1 diabetic mice by improving oxidative stress and inflammation in renal tubular epithelial cells
摘要
Abstract
Background Diabetic kidney disease(DKD)is one of the most serious vascular complications of diabetes mellitus and the main cause of end-stage renal disease.Long-term hyperglycemia leads to systemic oxidative stress and low-grade inflammation.Kaempferol,a natural flavonoid,has excellent anti-inflammatory and anti-oxidation abilities,and may play a role in the treatment of diabetic nephropathy.Objective To investigate the effects of kaempferol on renal injury and renal dysfunction in diabetic mice by reducing oxidative stress and inflammation.Methods Eighteen FVB mice aged 6-8 weeks were randomly divided into control group,diabetic model group and kaempferol gavage group.Type 1 diabetic mouse model was established by intraperitoneal injection of Streptozotocin(STZ).Blood glucose was measured every two weeks,and blood glucose over 16.6 mmol/L for two consecutive weeks was considered to be a successful diabetic model.After the model was established,the treatment group was given kaempferol(70mg/kg/d)by gavage,and the control group and the model group were given the same amount of CMC-Na by gavage.After 16 weeks for establishment of the model,the mice were sacrificed and the kidneys were obtained.The pathological injury of kidney was observed by pathological staining.qPCR and western blot were used to detect the mRNA expression of inflammatory factors and the expression of oxidative stress-related proteins in the kidney tissue of mice.The number and type of macrophages in the kidney were detected by flow cytometry.High glucose stimulated renal tubular epithelial cells(HK2)were used to establish a model of renal tubular injury in high glucose environment in vitro.The effect of different concentrations of kaempferol on the activity of HK2 was detected by CCK-8 kit.After high glucose stimulation and kaempferol treatment,ROS production in renal tubular epithelial cells was detected.The mRNA expression of inflammatory factors and the expression of oxidative stress-related proteins in HK2 were detected by qPCR and western blot.Results The results of animal experiments showed that compared with the diabetic model group,after gavage of kaempferol,the renal pathological damage was significantly improved,the glomerular mesangial proliferation and foot process fusion were reduced.The transcription levels of inflammatory factors such as IL-1β,IL-6 and TNF-α in kidney tissue decreased significantly.The expression of NADPH oxidase 4 was significantly decreased.The number of inflammatory macrophages in the kidney was significantly reduced,and the renal inflammatory microenvironment was improved.The results of cell experiments showed that kaempferol could inhibit the production of reactive oxygen species(ROS)in HK2 induced by high glucose,and it significantly improved the expression of oxidative stress-related protease,while the mRNA expression of related inflammatory factors was significantly reduced.Conclusion Kaempferol can significantly reduce oxidative stress and inflammation in diabetic kidney tissue,reduce the secretion of inflammatory factors induced by high glucose,and increase the expression of related oxidoreductase in HK2,which may alleviate diabetic kidney injury through HO-1/p38 pathway.关键词
山柰酚/肾小管上皮细胞/氧化应激/炎症/HO-1/p38通路/糖尿病肾病Key words
kaempferol/renal tubular epithelial cell/oxidative stress/inflammation/HO-1/p38 pathway/diabetic nephropathy分类
医药卫生引用本文复制引用
王超,魏翠婷,李润,佟琰,王雪,吴娇,欧阳清,陈香美..山柰酚通过改善肾小管上皮细胞的氧化应激与炎症反应减轻1型糖尿病小鼠肾损伤[J].解放军医学院学报,2024,45(3):261-269,9.基金项目
国家自然科学基金项目(32141005) （32141005）
