The anti-inflammatory activity of resveratrol in acute kidney injury: a systematic review and meta-analysis of animal studies.

CONTEXT: Accumulated experimental evidence suggests that resveratrol (RSV) may have an effect on acute kidney injury (AKI) by inhibiting inflammation. However, the credibility of the evidence for this practice is unclear. OBJECTIVE: This study investigated the effect of RSV on AKI and the underlying mechanism. METHODS: We searched PubMed, EMBASE, and Web of Science from 2005 to April 2022 for controlled animal trials assessing the effect of conventional resveratrol versus placebo on renal function outcome after AKI. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42022329596. RESULTS: We retrieved 455 studies, 25 studies comprising data of 436 animals that met the inclusion criteria. Our meta-analysis suggested that RSV treatment was significantly associated with lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The greatest effects were recorded in low-dose (<20 mg/kg/day) groups rather than in high-dose (> 20 mg/kg/day) groups. For time-response effects, subgroup analysis indicated that intervention duration of RSV can influence the treatment effect, and more beneficial effects were observed when studies had a drug administration time of <2 weeks. DISCUSSION AND CONCLUSIONS: This systematic review of animal AKI studies showed a consistently favourable effect of RSV as compared to placebo on renal function outcomes that increased with lower TNF-α, IL-6, and IL-1ß. RSV has a more beneficial effect on SA-AKI animal models than the others. When the RSV intervention dose was low (< 20 mg/kg/day) and the intervention time was <2 weeks, more benefits could be observed.

Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies.

BACKGROUND: Recommended regular saline flushing presents clinical ineffectiveness for hemodialysis (HD) patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has previously been used with a Ca2+ containing dialysate with prefiltered citrate in one arm (RCA-one). However, anticoagulation is not always achievable and up to 40% results in serious clotting in the venous expansion chamber. In this study, we have transferred one-quarter of the TSC from the prefiltered to the post filter based on RCA-one, which we have called RCA-two. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk. METHOD: In this investigator-initiated, multicenter, controlled, prospective, randomized clinical trial, 52 HD patients (77 sessions) were randomized to the RCA-2 and RCA-one group in part one of the trial, and 45 patients (64 sessions) were randomized to the RCA-2 and saline group in part two of the trial. Serious clotting events, adverse events and blood analyses were recorded. RESULTS: Serious clotting events in the RCA-two group were significantly lower compared with the RCA-one and saline group (7.89% vs. 30.77%, P = 0.011; 3.03% vs. 54.84%, P < 0.001, respectively). The median circuit survival time was 240 min (IQR 240 to 240) in the RCA-two group, was significantly longer than 230 min (IQR 155 to 240, P < 0.001) in the RCA-one group and 210 min (IQR 135 to 240, P = 0.003) in the saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the saline group and 10 patients (26.31%) in the RCA-two group, P > 0.05. CONCLUSIONS: Our data demonstrated that the modified anticoagulation protocol was more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. TRIAL REGISTRATION: GDREC, GDREC2017250H. Registered February 2, 2018; retrospectively registered.

Effectiveness of antiplatelet drugs for the prevention of diabetic nephropathy: A meta-analysis of randomized controlled trials
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AIMS: To evaluate the effects of antiplatelet drugs on proteinuria, renal function, and blood pressure (BP) in patients with diabetic nephropathy (DN). MATERIALS AND METHODS: A meta-analysis of randomized controlled trials (RCTs) was performed. Relevant RCTs were identified by a systematic search of the PubMed, Cochrane Library, and Embase databases. A random-effects model was applied to pool the results. RESULTS: Antiplatelet drugs significantly reduced urinary albumin excretion (weighted mean difference (WMD) = -69.25 mg/24, p = 0.005) and the urinary albumin/creatinine ratio (standardized mean difference (SMD) = -0.33, p = 0.009). However, renal function as reflected by the estimated glomerular filtration rate (WMD = -1.15 mL/min/1.73m2, p = 0.46) and BP (systolic BP: WMD = 1.53 mmHg, p = 0.35; diastolic BP: WMD = 0.40 mmHg, p = 0.70) were not significantly affected by antiplatelet drugs within 12 months of use (p > 0.05). CONCLUSION: Antiplatelet drugs may benefit patients with DN by reducing proteinuria. The long-term effects of antiplatelet drugs on the progression of DN warrant further evaluation.
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[Treatment of chronic primary glomerulopathy patients of Shen deficiency and dampness heat syndrome by yishen qingli granule combined low-dose Tripterygium wilfordii multiglycoside tablet: a clinical efficacy observation].

OBJECTIVE: To evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT). METHODS: Totally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed. RESULTS: Compared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05). CONCLUSION: On the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Idiopathic cholesterol crystal embolism with atheroembolic renal disease and blue toes syndrome: A case report.

BACKGROUND: Cholesterol crystal embolization (CCE) is a multisystemic and fatal disease with multiple clinical manifestations; however, there are few cases of idiopathic CCE. Here we report a patient with idiopathic CCE accompanied by atheroembolic renal disease and blue toes who had a relatively good prognosis in the short-term due to early treatment with corticosteroids and statins. CASE SUMMARY: A 76-year-old man complained of coldness, numbness and purple color change in his left foot for 7 d. He had a feeling of fatigue, constipation, foamy urine, poor appetite and sleep. He had a lacunar infarction for 5 years and hypertension for 9 mo. Laboratory results showed elevated eosinophils, cholesterol, uric acid, serum creatinine, urea and 24 h urine analysis revealed proteinuria. A renal biopsy revealed atheroembolic renal disease. Taken together, these findings strongly supported the diagnosis of idiopathic CCE and atheroembolic renal disease. CONCLUSION: Atheroembolic renal disease and blue toes syndrome can be caused by idiopathic CCE, and early treatment with corticosteroids is effective but requires further investigation.

Icariin Attenuation of Diabetic Kidney Disease Through Inhibition of Endoplasmic Reticulum Stress via G Protein-Coupled Estrogen Receptors.

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and has become the primary cause of End-Stage Renal Disease (ESRD) globally. Icariin (ICA), an effective component extracted from Epimedium, has antiosteoporosis effect, antitumor effects, anti-ischemia effects, and other effects. In this study, a mouse DKD model was established, and Icariin solid nanoliposomes were administered to determine whether ICA had a protective effect on the renal function of DKD mice by regulating estrogen level and endoplasmic reticulum (ER) stress pathway. The results showed that the microalbumin/creatinine in urine, serum urea nitrogen, and CHOL in ICA cultured DKD mice significantly decreased, and mice nephropathy improved significantly. rat renal tubule epithelial cells were further tested, and the rat renal tubule epithelial cells were modeled by cultured cells with high glucose. The results showed that high glucose could promote the proliferation of renal tubular epithelial cells. Simultaneously, ICA can inhibit the proliferation of renal tubular epithelial cells and induce cell apoptosis. Furthermore, the expression of ER stress-related proteins IRE1 and XBP-1S was further detected. Additionally, to ICA intervention, a GPER antagonist (G-15) was added for intervention, the inhibitory effects of IRE1 and XBP-1S were reversed, and the ER stress pathway was activated. Cell experiments showed that ICA could promote GPER expression, while inhibiting GPER expression promoted the activation of ER stress pathway, and GPER expression was negatively correlated with ER stress protein expression. Therefore, the experiment proved that in DKD tissues, a high concentration of ICA can inhibit the ER stress response by promoting the expression of GPER, reducing the proliferation of diabetic nephropathy, and increasing the rate of tissue apoptosis.

Quercetin alleviates chronic renal failure by targeting the PI3k/Akt pathway.

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.

Knockdown of the Long Noncoding RNA LUCAT1 Inhibits High-Glucose-Induced Epithelial-Mesenchymal Transition through the miR-199a-5p-ZEB1 Axis in Human Renal Tubular Epithelial Cells.

Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.

Large cutaneous epithelioid angiomatous nodules in a patient with nephrotic syndrome: A case report.

BACKGROUND: Cutaneous epithelioid angiomatous nodules (CEAN) are rare, benign, vascular lesions characterized by benign proliferation of endothelial cells with prominent epithelioid features, which can be easily confused with benign and malignant vascular tumors. However, the etiology of CEAN remains unclear, and no association with infection, trauma, or immunosuppression has been described. This case study indicated that CEAN is closely related to the patient's impaired immune status and may be induced by cyclosporine. CASE SUMMARY: A 19-year-old boy with nephrotic syndrome (NS) developed large CEAN on the left foot during treatment for NS. He had repeated relapses of edema in the past 6 years and different types of immunosuppressants were administered including methylprednisolone, mycophenolate mofetil, tacrolimus and cyclosporine; the dosages of these drugs were frequently adjusted. The patient had been receiving cyclosporine and methylprednisolone for 7 mo before he developed CEAN. Cyclosporine was discontinued due to its side effects on skin. After cessation of cyclosporine and 16 mo follow-up, the nodules gradually disappeared without any other treatment for the CEAN. CONCLUSION: Impaired immune status is proposed to be a risk factor for CEAN, which may be induced by cyclosporine.

Wenyang Lishui Decoction Ameliorates Podocyte Injury in Membranous Nephropathy Rat and Cell Models by Regulating p53 and Bcl-2.

Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study in vitro showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. MN rat models were induced by cationic bovine serum albumin. Experimental rats were divided into four groups: normal, model, WYD, and benazepril. The normal group consisted of normal rats receiving distilled water for four weeks, while the model, WYD, and benazepril groups consisted of MN rats receiving distilled water, 16.5 g/kg/day WYD aqueous extract, and 10 mg/kg/day benazepril, respectively. Alanine aminotransferase, kidney function, albumin, and 24 h urine total protein (UTP) were measured. Hematoxylin-eosin and electron microscopy analyses were performed. Mouse podocytes were induced to develop cell models by serum from IMN patients with antibody to the M-type phospholipase A2 receptor and spleen and kidney Yang deficiency syndrome. They were divided into five groups: control, model, 2 mg/ml WYD, 4 mg/ml WYD, and 8 mg/ml WYD. CCK-8 assays, flow cytometry, qRT-PCR, and Western blot analyses were performed. In the animal experiment, side effects of WYD were not found. Also, there was no significant difference in kidney function among the groups. In addition, UTP level was significantly reduced, and kidney histological damage was restored in both WYD and benazepril groups but difference in UTP level between them was not found. In the cell experiment, apoptosis rate was increased in the model group while it was decreased by coincubation with WYD. Besides, mRNA and protein levels of p53 were decreased, and those of Bcl-2 were increased by treatment using WYD. In conclusion, WYD could reduce proteinuria and ameliorate podocyte injury by regulating the expression of p53 and Bcl-2. The study is registered in the Chinese Clinical Trial Registry (ChiCTR-OCH-14005137).

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: -2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: -4.03,-0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

Effect of shenyan xiaobai granule on nephrin and podocin of adriamycin-induced renal injury: A randomised controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: ShenYanXiaoBai granules is a traditional Chinese herbal medicine, It is used widely for the treatment of proteinuria caused by various kidney diseases. AIM OF THE STUDY: This study investigated the mechanism of Shenyan Xiaobai Granule in the treatment of nephritis proteinuria. MATERIALS AND METHODS: 100 male wistar rats were divided into a blank group (n = 20) and a nephropathy group (n = 80) using random number table after 1 week adaptive feeded. Rats were injected with adriamycin (6.5 mg/kg) via the tail vein to induce nephropathy except for blank group. Every rat's urine protein was checked with urine protein dipstick test after three days that showed all rats in nephropathy group were successful modelled. Nephropathy group was divided into model group, benazepril group, ShenYanXiaoBai low dose group, ShenYanXiaoBai high dose group equally. Blank and model group were given distilled water 2 ml as control, then benazepril group received benazepril 0.90 mg/kg, ShenYanXiaoBai low dose group received ShenYanXiaoBai granules 1.80 g/kg as high dose group was given 3.60 g/kg, gavage for 6 days a week last for seven weeks. Urinary albumin/urinary creatinine were measured in seventh day every week. Three rats were randomly selected from each group to be executed in 3th and 5th weekend to detect the mRNA and protein expression level in kidney. The rest rats were as well. CONCLUSIONS: The therapeutic effect of ShenYanXiaoBai high dose group was better than the two other treated groups from the 5th week to the 7th week, the comparison had a significant difference. The therapeutic effect of benazepril group was better than the ShenYanXiaoBai low dose group in the 7 weeks and the comparison had a significant difference.

Annexin A2 and FTH1 are potential biomarkers for lupus nephritis.

Lupus nephritis (LN) occurs in ~50% of patients with systemic lupus erythematosus and is a major cause of morbidity and mortality of the affected individuals. Therefore, identification of novel and predictive biomarkers for the early diagnosis and progression of LN is required. The present study included 10 patients with LN whose diagnoses were confirmed by renal biopsy and 5 healthy participants as control subjects. Sera were collected both from patients with LN and healthy controls. Subsequently, mesangial cells were treated with these sera for 24 h. Differential proteins between groups were detected by two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis. 2D-DIGE maps of cellar proteins were obtained for LN and normal control groups. A total of 45 proteins were characterized, and 2 low-abundance proteins were identified. Compared with the normal human sera group, expression level of Annexin A2 was elevated in patients with LN, while the expression of the ferritin heavy chain (FTH1) decreased in the LN group; the analysis was carried out by DeCyder version 7.0 automatically. The results of the present study suggest that Annexin A2 and FTH1 contributed to the progression of LN and could serve as potential biomarkers for this disease.

Role of the TGFß/p65 pathway in tanshinone â ¡A-treated HBZY­1 cells.

Tanshinone â…¡A (TⅡA) is widely used for the treatment of a number human diseases, including diabetic nephropathy (DN) (1). The present study was performed to examine the role of the transforming growth factor ß (TGFß)/p65 pathway under TⅡA treatment in a glomerular mesangial cell model of DN. Firstly, it was identified that TⅡA inhibited the proliferation of HBZY­1 cells, while simultaneously suppressing the expression of TGFß and p65. In addition, glucose-induced HBZY­1 cells were treated with TⅡA, si­TGFß and si­p65. The results revealed that si­TGFß or si­p65 were able to inhibit the proliferation of HBZY­1 cells as well. Finally, the expression of TGFß and p65 in a rat model of DN treated with TⅡA was detected. The results demonstrated that renal hypertrophy and 24 h urinary protein excretion were ameliorated in TⅡA-treated rats with DN. Furthermore, it was revealed that the protein levels of TGFß and p65 were decreased in the DN rats following TⅡA treatment. In conclusion, the present study demonstrated that TGFß and p65 were activated by TⅡA in HBZY­1 cells. In addition, the expression of TGFß and of p65 was downregulated in rats with DN treated with TⅡA.