OBJECTIVEMatrine has an anti-fibrosis effect, such as hepatic cirrhosis and derma fibrosis, while its effect on glomerulosclerosis is unknown. The purpose of this study was to analyze the renoprotective effects of matrine on experimental glomerulosclerosis in rats and inquire into its mechanisms.

METHODSThe rats were randomly assigned to following groups: normal control group, model control group, benazepril treatment group, matrine 100 mg/kg treatment group and matrine 50 mg/kg treatment group. The rats of normal control group were subjected to sham operation and were injected with normal saline via the tail vein one week later. The rats of the other groups were uninephrectomized and injected with adriamycin (5 mg/kg) via the tail vein one week later. The dose of benazepril was 6 mg/kg. Both matrine and benazepril were given by gastric perfusion from the first day after the operation. The level of urinary protein was measured at the 2nd, 4th and 6th week after the operation. The serum total protein and albumin, serum creatinine, blood urea nitrogen (BUN) were tested only at the 6th week after operation. Renal pathology changes were evaluated at the 6th week as well. Immunohistochemistry was used to detect the expression of fibronectin (FN), laminin (LN), connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-beta1) in glomeruli.

RESULTSMatrine and benazepril not only reduced the excretion of urinary protein and the level of serum creatinine and BUN, but also significantly ameliorated glomerular mesangial proliferation and glomerular sclerosis (P < 0.05, respectively). Immunohistochemical staining indicated that there was an increasing FN, LN, CTGF and TGF-beta1 expression in model control group as compared to the three treatment groups (P < 0.05). Matrine 100 mg/kg treatment group and benazepril treatment group showed much more advantages than matrine 50 mg/kg treatment group (P < 0.05), but there was no significant difference between the former two groups (P > 0.05).

CONCLUSIONMatrine has a renoprotective effect on experimental glomerulosclerosis in rats, the possible mechanism might relate to the reduction of the TGF-beta1 negative function via CTGF, which will inhibit the activation and proliferation of glomerular intrinsic cells, decrease the secretion of ECM accordingly.

Alkaloids ; pharmacology ; Animals ; Benzazepines ; pharmacology ; Kidney ; drug effects ; Kidney Diseases ; prevention & control ; Kidney Glomerulus ; drug effects ; Protective Agents ; pharmacology ; Quinolizines ; pharmacology ; Rats ; Renal Agents ; pharmacology

Animals ; Disease Progression ; Kidney Diseases ; physiopathology ; Kidney Glomerulus ; drug effects ; pathology ; Rats ; Renal Agents ; pharmacology ; Renin-Angiotensin System ; drug effects ; Sclerosis

OBJECTIVETo investigate the increased podocyte permeability by evidence of adriamycin (AD) and its molecular mechanism.

METHODSIn this study, we explored the direct effects of AD on cultured mouse podocytes and the potential protection effects of Dexamethasome (Dex).

RESULTSAfter 24-hour AD (5 x 10(-7) mol/L) treatment, albumin passage through podocyte monolayers was increased by 2.27-fold (P < 0.01). AD caused a 62% decrease in Zonula Occluden-1 (ZO-1) protein (P < 0.05), suggesting that AD might increase podocyte permeability by disrupting tight junctions. Dex (1 x 10(-6) mol/L), co-administered with AD, protected podocytes from AD-induced increased albumin passage. This may be linked with an increased P-cadherin protein level to 1.93 fold of control (P < 0.01).

CONCLUSIONSAD has a direct, detrimental effect on podocyte permeability, probably through disrupting tight junctions; Dex could protect against AD-induced high podocyte permeability by upregulating adherent protein P-cadherin.

Albumins ; metabolism ; Animals ; Cadherins ; analysis ; Cell Membrane Permeability ; drug effects ; Cells, Cultured ; Dexamethasone ; pharmacology ; Doxorubicin ; pharmacology ; Epithelial Cells ; drug effects ; Kidney Glomerulus ; cytology ; drug effects ; Mice

OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.
Animal ; Basement Membrane/pathology ; Basement Membrane/metabolism ; Basement Membrane/drug effects ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/chemically induced* ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/drug effects ; Male ; Phenylurea Compounds/toxicity* ; Proteochondroitin Sulfates/metabolism ; Rats ; Rats, Wistar

OBJECTIVETo compare the serum miR-663 levels in renal transplant patients with and without acute rejection (AR) and explore the role of miR-663 acute renal graft rejection.

METHODSReal time-PCR was used to determine serum miR-663 levels in renal transplant recipients with and without AR. MTT assay and Annexin V-FITC assay were employed to examine the viability and apoptosis of human renal glomerular endothelial cells (HRGEC) treated with a miR-663 mimic or a miR-663 inhibitor, and ELISA was performed to detect the expression of inflammation-related cytokines including IL-6, IFN-γ, CCL-2 and TNF-α in the cells. Transwell assay was used to examine the effect of miR-663 mimic and miR-663 inhibitor on the chemotactic capability of macrophages.

RESULTSSerum miR-663 level was significantly higher in renal transplant recipients with AR than in those without AR. The miR-663 mimic significantly inhibited the viability of HRGECs and increase the cell apoptosis rate, while miR-663 inhibitor suppressed the cell apoptosis. The miR-663 mimic increased the expression levels of inflammation-related cytokines and enhanced the chemotactic capability of macrophages.

CONCLUSIONmiR-663 might play important roles in acute renal graft rejection and may become a therapeutic target for treating AR.

Apoptosis ; Cells, Cultured ; Cytokines ; metabolism ; Endothelial Cells ; cytology ; Graft Rejection ; blood ; Humans ; Kidney Glomerulus ; cytology ; Kidney Transplantation ; Macrophages ; cytology ; drug effects ; MicroRNAs ; blood

OBJECTIVETo investigate the effect of qianjin huanglian pill on kidney in monosodium L-glutamate (MSG)-treated insulin resistance (IR) mice.

METHODThe ameliorative effect of qianjin huanglian pill on IR in MSG mice was evaluated in comparison with rosiglitazone (Ros). The fasting serum glucose, fasting serum insulin, insulin sensitivity index, urinary albumin excretion, glomerular diameter and pathological changes of kidney were investigated in the evaluation.

RESULTAfter 2 weeks of qianjin huanglian pill treatment, the urinary albumin excretion (UAE) was reduced in low-dose group (P < 0.05) as compared with the model group. After 4 weeks of qianjin huanglian pill treatment, the fasting serum glucose was reduced in high-dose group (P < 0.001 compared with the model group). ISI of mice was ameliorated in high-dose group (P < 0.05 compared with the model group). The glomerular diameter was decreased, the hyperplasia of glomerulus was ameliorated in high-dose and low-dose groups (P < 0.01 compared with model group).

CONCLUSIONIn MSG mice, we found qianjin huanglian pill could increase insulin sensitivity, decrease the urinary albumin excretion, ameliorate the pathological changes of kidney due to insulin resistance.

Animals ; Blood Glucose ; metabolism ; Chemistry, Pharmaceutical ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Insulin Resistance ; Kidney ; drug effects ; pathology ; Kidney Glomerulus ; drug effects ; pathology ; Male ; Mice ; Sodium Glutamate ; toxicity

Previously, we reported that high glucose enhanced cytokine-induced nitric oxide (NO) production by rat mesangial cells (MCs), and that the enhanced expression of the iNOS pathway may promote extracellular matrix accumulation by MCs. The present study was designed to examine whether the iNOS pathway is pathologically altered in experimental diabetic nephropathy, and whether therapy with angiotensin converting enzyme (ACE) inhibitor (imidapril: I) or angiotensin II type I receptor (AT1) blocker (L-158,809: L), ameliorates these changes. Male Sprague-Dawley rats were injected with diluent (control: C) or streptozotocin. At sacrifice after 4, 8 and 12 weeks, rats underwent either a 4 hour placebo or an intraperitoneal lipopolysaccharide (LPS, 2 mg/kg) challenge. Systolic blood pressure (SBP) and urinary protein excretion (UPE) increased significantly in diabetic (D) rats compared with C. The basal expression of glomerular iNOS mRNA was increased in D rats compared with that of C rats, by reverse- transcription (RT)-polymerase chain reaction (PCR), whereas there was no significant difference in the level of protein by Western blot analysis. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation, of LPS-stimulated iNOS expression, was equally ameliorated both by I and L in mRNA and protein levels. From immunohistochemistry (IHC), there was a negative staining for the iNOS within the glomeruli of five C rats without LPS treatment, but one of four rats, with LPS treatment, showed minimal iNOS staining in the glomeruli. In D rats, the glomerular mesangium and podocytes were positive for iNOS in each of three out of five rats with, and without, LPS treatment. In conclusion, LPS-stimulated glomerular iNOS expression was enhanced in diabetic pnephropathy, and the activation of angiotensin II may play a role in this enhancement.
Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animal ; Kidney Glomerulus/*drug effects/*enzymology ; Lipopolysaccharides/*pharmacology ; Male ; Nitric-Oxide Synthase/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Angiotensin/antagonists & inhibitors

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertrophy ; drug therapy ; enzymology ; genetics ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

OBJECTIVESTo explore the effects and significance of Huanshuai Recipe Oral Liquid (, HSR), a formula with supplementing qi, nourishing blood and activating blood on restructuring glomerular microvasculature and expression of vascular endothelial growth factor (VEGF) in subtotal nephrectomized (SNX) rats.

METHODSA total of 76 male Wistar rats were randomly divided into four groups: 16 in the sham-operated group and fed with tap water 10 mL/kg per day; 20 in the model group were operated with 5/6 SNX and fed with tap water 10 mL/ kg per day; 20 SNX rats in the HSR group were treated with HSR 10 mL/kg per day; 20 SNX rats in the losartan group were treated with losartan 40 mg/kg per day. Serum creatinine (SCr) and urinary protein excretion (Upro) were examined at the 2nd, 4th, 8th, and 12th weeks of the treatment, and the remnant kidneys were harvested. Changes in histological microstructure were evaluated using light microscopy, and the expression of VEGF was detected by using ELISA.

RESULTSUpro, microvasculature injury and glomerulosclerosis were found to be alleviated in HSR and Losartan groups, respectively. The change of VEGF expression showed positive correlation with glomerular capillary area and peritubular capillary number (r=0.448, r=0.422, P<0.01), but negative correlation with that of SCr and Upro (r=-0.592, r=-0.481, P<0.01).

CONCLUSIONSHSR could regulate the VEGF expression, reduce the loss of microvasculature, which demonstrated similar renal protective effects to losartan in SNX rats. Examination of Chinese herbal medicine influence on VEGF signaling and restructuring renal microvasculature may elucidate the molecular mechanism of renal protection to a certain degree.

Administration, Oral ; Animals ; Capillaries ; drug effects ; metabolism ; pathology ; Collagen Type IV ; metabolism ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Extracellular Matrix ; drug effects ; metabolism ; Fibronectins ; metabolism ; Immunohistochemistry ; Kidney Cortex ; drug effects ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; blood supply ; drug effects ; pathology ; physiopathology ; Microvessels ; drug effects ; Nephrectomy ; Proteinuria ; blood ; drug therapy ; physiopathology ; Rats ; Rats, Wistar ; Time Factors ; Vascular Endothelial Growth Factor A ; metabolism

There are several reports to demonstrate that rifampicin, a major anti-tuberculosis agent, is associated with some adverse renal effects, with a few cases of rifampicin-induced minimal change disease (MCD). In the present case, a 68-year-old female presented with nausea, vomiting, foamy urine, general weakness and edema. She had been taking rifampicin for 4 weeks due to pleural tuberculosis. The patient had no proteinuria before the anti-tuberculosis agents were started, but urine tests upon admission showed heavy proteinuria with a 24-h urinary protein of 9.2 g/day, and serum creatinine, albumin, and total cholesterol levels were 1.36 mg/dL, 2.40 g/dL, and 283 mg/dL, respectively. MCD was diagnosed, and the patient achieved complete remission after cessation of rifampicin without undergoing steroid therapy.
Aged ; Antibiotics, Antitubercular/*adverse effects/therapeutic use ; Edema/etiology ; Female ; Humans ; Kidney Function Tests ; Kidney Glomerulus/pathology ; Nausea/etiology ; Nephrosis, Lipoid/*chemically induced/pathology ; Proteinuria ; Remission Induction ; Rifampin/*adverse effects/therapeutic use ; Treatment Outcome ; Tuberculosis, Pleural/*drug therapy