1.Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease.
Xu WANG ; Yue ZHANG ; Hongwei LI ; Handong LIU ; Jie LI ; Ying FAN ; Zhilong ZHANG
Chinese Acupuncture & Moxibustion 2025;45(10):1450-1458
OBJECTIVE:
To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein.
METHODS:
A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR.
RESULTS:
After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01).
CONCLUSION
The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals
;
Podocytes/cytology*
;
Diabetic Nephropathies/physiopathology*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Mechanistic Target of Rapamycin Complex 1/genetics*
;
Autophagy
;
Acupuncture Therapy
;
Autophagy-Related Protein-1 Homolog/genetics*
;
RNA, Long Noncoding/metabolism*
;
Humans
;
Signal Transduction
2.Bioinformatics analysis of efferocytosis-related genes in diabetic kidney disease and screening of targeted traditional Chinese medicine.
Yi KANG ; Qian JIN ; Xue-Zhe WANG ; Meng-Qi ZHOU ; Hui-Juan ZHENG ; Dan-Wen LI ; Jie LYU ; Yao-Xian WANG
China Journal of Chinese Materia Medica 2025;50(14):4037-4052
This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans
;
Computational Biology
;
Diabetic Nephropathies/physiopathology*
;
Protein Interaction Maps
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal
;
Phagocytosis/genetics*
;
Efferocytosis
3.Effects and mechanisms of total flavones of Abelmoschus manihot combined with empagliflozin in attenuating diabetic tubulopathy through multiple targets based on mitochondrial homeostasis and ZBP1-mediated PANoptosis.
Si-Yu CHA ; Meng WANG ; Yi-Gang WAN ; Si-Ping DING ; Yu WANG ; Shi-Yu SHEN ; Wei WU ; Ying-Lu LIU ; Qi-Jun FANG ; Yue TU ; Hai-Tao TANG
China Journal of Chinese Materia Medica 2025;50(13):3738-3753
This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals
;
Rats
;
Mitochondria/metabolism*
;
Benzhydryl Compounds/administration & dosage*
;
Glucosides/administration & dosage*
;
Abelmoschus/chemistry*
;
Male
;
Homeostasis/drug effects*
;
Flavones/administration & dosage*
;
Rats, Sprague-Dawley
;
Diabetic Nephropathies/physiopathology*
;
Drugs, Chinese Herbal/administration & dosage*
;
DNA-Binding Proteins/genetics*
;
Humans
;
Apoptosis/drug effects*
4.Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells.
Biqiong FU ; Jie YANG ; Jia CHEN ; Lirong LIN ; Kehong CHEN ; Weiwei ZHANG ; Jianguo ZHANG ; Yani HE
Frontiers of Medicine 2019;13(2):267-276
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16 and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor-g in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.
Animals
;
Cells, Cultured
;
Cellular Senescence
;
drug effects
;
Cyclin D1
;
metabolism
;
Cyclin-Dependent Kinase Inhibitor p16
;
metabolism
;
Diabetic Nephropathies
;
drug therapy
;
Drugs, Chinese Herbal
;
pharmacology
;
Epithelial Cells
;
drug effects
;
metabolism
;
Glucose
;
Kidney Tubules, Proximal
;
physiopathology
;
Male
;
Mice
;
Mice, Inbred C57BL
5.Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy.
Shun-Jin HU ; Bing SHU ; Hua JIN ; Xiao-Feng LI ; Jia-Rong MAO ; Ke-Jun REN ; Lei GAO ; Li YANG ; You-Wan WU ; Yong-Jun WANG
Chinese journal of integrative medicine 2018;24(8):600-605
OBJECTIVETo evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN).
METHODSForty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.
RESULTSCompared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).
CONCLUSIONSTangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.
Albuminuria ; complications ; Animals ; Basement Membrane ; drug effects ; metabolism ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; urine ; Diabetic Nephropathies ; blood ; drug therapy ; physiopathology ; urine ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; Kidney Function Tests ; Kidney Glomerulus ; drug effects ; pathology ; physiopathology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Male ; Rats, Sprague-Dawley
6.Effects of centella asiatica granule on the expression of TGF-β and related down-stream signals in rats with early diabetic nephropathy.
Ji-Wei MA ; Hong-Tian WANG ; Hao-Fei LIU ; Yuan DING ; Ji-Qiong BAI ; Zhu ZHANG
Chinese Journal of Applied Physiology 2018;34(1):69-73
OBJECTIVE:
To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals.
METHODS:
Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.
RESULTS:
The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN.
CONCLUSIONS
CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals
;
Centella
;
chemistry
;
Diabetes Mellitus, Experimental
;
Diabetic Nephropathies
;
chemically induced
;
drug therapy
;
metabolism
;
Drugs, Chinese Herbal
;
pharmacology
;
Kidney
;
physiopathology
;
Male
;
Rats
;
Rats, Sprague-Dawley
;
Receptor, Transforming Growth Factor-beta Type I
;
metabolism
;
Receptor, Transforming Growth Factor-beta Type II
;
metabolism
;
Signal Transduction
;
Smad2 Protein
;
metabolism
;
Smad3 Protein
;
metabolism
;
Smad7 Protein
;
metabolism
;
Transforming Growth Factor beta1
;
metabolism
7.The Impact of Diabetes Mellitus on Vascular Biomarkers in Patients with End-Stage Renal Disease.
Jeonggeun MOON ; Chan Joo LEE ; Sang Hak LEE ; Seok Min KANG ; Donghoon CHOI ; Tae Hyun YOO ; Sungha PARK
Yonsei Medical Journal 2017;58(1):75-81
PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients. MATERIALS AND METHODS: Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort. RESULTS: The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046). CONCLUSION: Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients.
Aged
;
Aorta
;
Biomarkers
;
Blood Pressure/physiology
;
Blood Pressure Monitoring, Ambulatory
;
Coronary Artery Disease/diagnostic imaging/*physiopathology
;
Diabetes Mellitus/*physiopathology
;
Diabetic Nephropathies/physiopathology
;
Echocardiography
;
Female
;
Humans
;
Kidney Failure, Chronic/*physiopathology
;
Male
;
Middle Aged
;
Pulse Wave Analysis
;
Regression Analysis
;
Risk Factors
;
Systole/physiology
8.Clinical Characteristics of Patients with Diabetic Nephropathy on Maintenance Hemodialysis: A Multicenter Cross-sectional Survey in Anhui Province, Eastern China.
Hu CHEN ; De-Guang WANG ; Liang YUAN ; Gui-Ling LIU ; Heng-Jie HE ; Juan WANG ; Sen ZHANG ; Li HAO
Chinese Medical Journal 2016;129(11):1291-1297
BACKGROUNDThe incidence of diabetic nephropathy (DN) increases year by year. However, clinical characteristics of DN patients on maintenance hemodialysis (MHD) were rarely reported in China. The purpose of this study was to examine the clinical characteristics of the DN patients on MHD in Anhui Province, Eastern China.
METHODSThe clinical data of MHD patients in the hemodialysis centers of 26 hospitals in Anhui Province from January 1, 2014, to March 31, 2014, were examined. The differences between DN patients and non-DN patients were compared regarding vascular access, nutritional status, mineral and bone disorder, and other indexes.
RESULTSAmong the selected 2768 adult MHD patients, 427 had DN. The incidence of hypertension, coronary heart disease, and cerebral thrombus in DN patients was 94.1%, 21.5%, and 15.0%, respectively, which were higher than those in non-DN patients (P < 0.001). Category of vascular access for hemodialysis in DN patients was arteriovenous fistula (AVF) (87.4% [373/427]) and tunneled cuffed catheter (TCC) (11.2% [48/427]). The percentage of AVF was significantly lower than that of non-DN patients (P < 0.001), and percentage of TCC was significantly higher than that of non-DN patients (P < 0.001). Hemoglobin achievement rate in DN patients was 32.0%. The incidence of hypoalbuminemia was 24.7%, significantly higher than that in non-DN patients (P < 0.001). The achievement rate of the target range in mineral values was 55.9% in corrected serum calcium level, 30.1% in serum phosphorus level, and 49.3% in intact parathyroid hormone (iPTH) level in DN patients. Compared with non-DN patients, the achievement rate of serum phosphorus was significantly higher in DN patients.
CONCLUSIONSDN patients on MHD in Anhui province exhibited different clinical characteristics compared to non-DN hemodialysis patients. They presented higher percentage in TCC use and cardiovascular complication, lower serum albumin and iPTH levels than those in non-DN patients.
Aged ; Calcium ; blood ; China ; Coronary Disease ; blood ; epidemiology ; physiopathology ; Cross-Sectional Studies ; Diabetic Nephropathies ; blood ; epidemiology ; physiopathology ; Female ; Humans ; Hypertension ; blood ; epidemiology ; physiopathology ; Intracranial Thrombosis ; blood ; epidemiology ; physiopathology ; Male ; Middle Aged ; Parathyroid Hormone ; blood ; Phosphorus ; blood ; Renal Dialysis
9.Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy.
Bo Hwan KIM ; Eun Soo LEE ; Ran CHOI ; Jarinyaporn NAWABOOT ; Mi Young LEE ; Eun Young LEE ; Hyeon Soo KIM ; Choon Hee CHUNG
Yonsei Medical Journal 2016;57(3):664-673
PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.
Albuminuria
;
Animals
;
Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
;
Curcumin/*pharmacology
;
Diabetes Mellitus, Type 2/*metabolism/urine
;
Diabetic Nephropathies/complications/*drug therapy/metabolism/pathology
;
Gene Expression/drug effects
;
Inflammation
;
Kidney/drug effects/metabolism/physiopathology
;
Kidney Glomerulus/metabolism/physiopathology
;
Lipid Metabolism/*drug effects
;
Male
;
Malondialdehyde/metabolism/urine
;
Oxidative Stress/*drug effects
;
Rats
;
Rats, Inbred OLETF
;
Rats, Long-Evans
;
Superoxide Dismutase/metabolism
10.Correlation between cognitive impairment and diabetic nephropathy in patients with Type 2 diabetes mellitus.
Xiajie SHI ; Yuren ZHANG ; Hongtao NIU ; Ran WANG ; Jinjing SHEN ; Shanlei ZHOU ; Haobo YANG ; Shan WANG ; Jing WU
Journal of Central South University(Medical Sciences) 2016;41(2):143-150
OBJECTIVE:
To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
METHODS:
Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
RESULTS:
1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
CONCLUSION
Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.
Adult
;
Aspartic Acid
;
analogs & derivatives
;
metabolism
;
Case-Control Studies
;
Cerebrum
;
metabolism
;
Choline
;
metabolism
;
Cognition
;
Cognition Disorders
;
epidemiology
;
Creatine
;
metabolism
;
Diabetes Mellitus, Type 2
;
physiopathology
;
Diabetic Nephropathies
;
epidemiology
;
Glomerular Filtration Rate
;
Humans
;
Neuropsychological Tests

Result Analysis
Print
Save
E-mail