OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:nor...OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:normal,model,Tongluo Digui decoction(high,medium,and low dose)and valsartan.Streptozotocin was injected intraperitoneally to replicate the diabetic animal model.After 8 weeks,proteinuria was evaluated to establish the diabetic nephropathy model.Treatments were administered daily via the intragastric route.At 16 weeks after gavage,we determined 24 h urine protein concentration,and blood glucose,serum creatinine,and urea nitrogen concentrations.Then,rats were sacrificed,and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli,including glomerular podocytes by transmission electron microscopy.Western blot analysis was used to determine the expression of nephrin,podocin,p62,beclin-1,LC3Ⅱ/Ⅰ,and p-m TOR/m TOR protein in kidney tissues.RESULTS:Compared with the model group,Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration,and blood glucose,hemoglobin A1 c,serum creatinine,urea nitrogen concentrations,total serum protein and albumin.Concurrently,mesangial mesenteric broadening and fusion of foot processes were reduced,the glomerular basement membrane was not significantly thickened,and the number of podocytes and the number of autophagosomes in the podocytes was increased.Further,expression of nephrin,podocin,LC3Ⅱ,and beclin-1 protein in kidney tissue was up-regulated,while expression of p62 protein was down-regulated and m TOR phosphorylation was inhibited.CONCLUSION:Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting m TOR phosphorylation,thereby increasing autophagy to protect podocytes and reducing proteinuria.展开更多
基金Supported by the funds of Key Scientific Research Project of Colleges and Universities in Henan Province in 2017(Explore the Mechanism of Huoxue Tongluo Decoction in Preventing and Treating Diabetic Nephropathy from the Regulation of Podocyte Autophagy by Mtor Signal Pathway,No.17A360003)the Research Project of National TCM Clinical Research Base(Project Number:2019jdzx068+9 种基金Project Name:Study on the Effect of Tongluo Digui Decoction on Circadian Rhythm of Diabetic Nephropathy Based on Lncrna-mrna Chip Technology)the Special Research Project of TCM In Henan Province(Project Number:2019zybj17Project Name:Study on the Mechanism of Tongluo Digui Decoction in the Treatment of Diabetic Kidney Disease by Regulating the Pyroptosis of Podocyte through Autophagy-related Molecular Pathways)Henan Province Key R&D and Promotion Special(Science and Technology)Project(Project Number:202102310505Project Name:Study on the Mechanism Of Tongluo Digui Decoction in the Treatment of Diabetic Nephropathy Based on Autophagy Regulating Renal Tubular Epithelial Cell Pyroptosis)Henan Province Key R&D and Promotion Special(Science and Technology)Project(Project Number:202102310171Project Name:to Explore the Mechanism of Tongluo Digui Decoction on Improving Non-dipper Blood Pressure In Diabetic Nephropathy Based on Circadian Rhythm)a Sub-station Project of the Inheritance Studio of Famous Old Chinese Medicine Experts Across the CountryTCM Top Talent Training Project of Henan ProvinceNational TCM Innovational Core Talent Training Project。
文摘OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:normal,model,Tongluo Digui decoction(high,medium,and low dose)and valsartan.Streptozotocin was injected intraperitoneally to replicate the diabetic animal model.After 8 weeks,proteinuria was evaluated to establish the diabetic nephropathy model.Treatments were administered daily via the intragastric route.At 16 weeks after gavage,we determined 24 h urine protein concentration,and blood glucose,serum creatinine,and urea nitrogen concentrations.Then,rats were sacrificed,and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli,including glomerular podocytes by transmission electron microscopy.Western blot analysis was used to determine the expression of nephrin,podocin,p62,beclin-1,LC3Ⅱ/Ⅰ,and p-m TOR/m TOR protein in kidney tissues.RESULTS:Compared with the model group,Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration,and blood glucose,hemoglobin A1 c,serum creatinine,urea nitrogen concentrations,total serum protein and albumin.Concurrently,mesangial mesenteric broadening and fusion of foot processes were reduced,the glomerular basement membrane was not significantly thickened,and the number of podocytes and the number of autophagosomes in the podocytes was increased.Further,expression of nephrin,podocin,LC3Ⅱ,and beclin-1 protein in kidney tissue was up-regulated,while expression of p62 protein was down-regulated and m TOR phosphorylation was inhibited.CONCLUSION:Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting m TOR phosphorylation,thereby increasing autophagy to protect podocytes and reducing proteinuria.
文摘目的观察健脾补肾地龟汤治疗慢性肾脏病(CKD)3~4期营养不良患者的疗效。方法选取CKD 3~4期营养不良患者90例,按随机数字表法分为对照组和治疗组各45例。2组均给予基础治疗。对照组加用复方α酮酸片治疗,每次4粒,每日3次;治疗组加用健脾补肾地龟汤,治疗2个月。观察治疗前后2组临床症状、SGA评分、肾功能、血清白蛋白(Alb)、血红蛋白(Hb)、C反应蛋白(CRP)、转铁蛋白(TF)、前白蛋白(PA)、红细胞(RBC)计数、网织红细胞(RET)绝对值等指标变化。结果与对照组相比,治疗组血肌酐(Scr)、24 h尿蛋白(24 h Upr)明显下降(P<0.01);营养不良状态明显改善;血清Alb、Hb明显升高(P<0.05);症状评分及SGA评分显著降低(P<0.05);CRP明显下降(P<0.05)。结论健脾补肾地龟汤能改善患者营养不良状况,保护肾功能,下调CRP水平。
