OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pa...OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pathogen free,SPF grade)were divided into five groups(n=6 per group):control,DKD model,DKD model with YSTLF(4.9 g/kg),DKD model with YSTLF(9.8 g/kg),and DKD model with captopril.DKD was induced through a single intraperitoneal injection of streptozotocin(150 mg/kg).Body weight,fasting blood glucose and urine C-peptide levels were measured to assess metabolic regulation by YSTLF.Renal function was evaluated using indicators of glomerular and tubular health.Liver function was assessed by measuring aspartate aminotransferase and alanine aminotransferase levels.Renal pathological changes were examined using hematoxylin/eosin staining and transmission electron microscopy.Inflammatory and apoptosis-related factors were analyzed through enzyme-linked immunosorbent assay,immunohistochemistry,and Western blot analysis.RESULTS:In DKD mice,fasting blood glucose,Cpeptide,24-hour urine protein(UP)levels,and renal damage were elevated,accompanied by increased inflammation and apoptosis.YSTLF significantly reduced 24-hour UP and C-peptide levels and improved kidney and liver function in DKD mice.YSTLF also mitigated glomerular hypertrophy,basement membrane thickening,and podocyte foot process effacement.It upregulated the expression of the podocyte marker podocalyxin.Furthermore,YSTLF alleviated inflammation and apoptosis,likely by reducing the overexpression of monocyte chemoattractant protein(MCP-1),Bax,and Caspase-3 in the kidneys of DKD mice.CONCLUSIONS:These findings suggest that YSTLF ameliorates kidney injury by modulating the expression of inflammatory cytokine MCP-1 and the Bax/Caspase-3 apoptosis pathway,providing a potential therapeutic approach for DKD.展开更多
基金National Key Research and Development Plan:Evidence-Based Evaluation and Therapeutic Mechanism Cooperation Study of Yishen Tongluo Formula for Preventing Diabetes Kidney Disease(Phase 3)(No.2020YFE0201800)Key Science and Technology Projects of Henan Province:Research on Innovative Drug Cooperation of Traditional Chinese Medicine Yishen Tongluo Concentrated Pills(益肾通络浓缩丸)(No.221111520300)+1 种基金Key scientific and technological projects of Henan province:Study on the Pharmacodynamic Mechanism of Yishen Tongluo Formula in Treatment of Diabetes Kidney Disease based on the Interaction Regulation of Protein Phosphorylation and Acylation Modification(No.212102310347)to WU SuhuiNational Natural Science Foundation of China:the Mechanism of Yishen Tongluo Formula Intervention in Diabetic Kidney Disease based on(Yin-Yang-1/Nuclear Factor Erythroid 2-Related Factor 2 Mediated Endothelial Podocyte Interaction Response(No.82474495)to XU Jiangyan。
文摘OBJECTIVE:To investigate the effect and mechanism of Yishen Tongluo formula(益肾通络方,YSTLF)in streptozotocin-induced diabetic kidney disease mice(DKD)mice.METHODS:Thirty Institute of Cancer Research mice(specific pathogen free,SPF grade)were divided into five groups(n=6 per group):control,DKD model,DKD model with YSTLF(4.9 g/kg),DKD model with YSTLF(9.8 g/kg),and DKD model with captopril.DKD was induced through a single intraperitoneal injection of streptozotocin(150 mg/kg).Body weight,fasting blood glucose and urine C-peptide levels were measured to assess metabolic regulation by YSTLF.Renal function was evaluated using indicators of glomerular and tubular health.Liver function was assessed by measuring aspartate aminotransferase and alanine aminotransferase levels.Renal pathological changes were examined using hematoxylin/eosin staining and transmission electron microscopy.Inflammatory and apoptosis-related factors were analyzed through enzyme-linked immunosorbent assay,immunohistochemistry,and Western blot analysis.RESULTS:In DKD mice,fasting blood glucose,Cpeptide,24-hour urine protein(UP)levels,and renal damage were elevated,accompanied by increased inflammation and apoptosis.YSTLF significantly reduced 24-hour UP and C-peptide levels and improved kidney and liver function in DKD mice.YSTLF also mitigated glomerular hypertrophy,basement membrane thickening,and podocyte foot process effacement.It upregulated the expression of the podocyte marker podocalyxin.Furthermore,YSTLF alleviated inflammation and apoptosis,likely by reducing the overexpression of monocyte chemoattractant protein(MCP-1),Bax,and Caspase-3 in the kidneys of DKD mice.CONCLUSIONS:These findings suggest that YSTLF ameliorates kidney injury by modulating the expression of inflammatory cytokine MCP-1 and the Bax/Caspase-3 apoptosis pathway,providing a potential therapeutic approach for DKD.
