OBJECTIVETo observe the effect of Cordyceps sinensis (CS) powder on renal oxidative stress and mitochondria functions in 5/6 nephrectomized rats, and to primarily explore its possible mechanisms.

METHODSTotally 30 male Sprague-Dawley rats were divided into the sham-operation group, the model group, and the treatment group by random digit table, 10 in each group. A chronic kidney disease (CKD) rat model was prepared by one step 5/6 nephrectomy. Rats in the treatment group were intragastrically administered with CS powder solution at the daily dose of 2 g/kg, once per day. Equal volume of double distilled water was intragastrically administered to rats in the sham-operation group and the model group. All medication lasted for 12 weeks. The general condition of rats, their body weight, blood pressure, 24 h proteinuria, urinary N-acetyl-β-D-glucosaminidase (NAG), serum creatinine (SCr) , and blood urea nitrogen (BUN) were assessed before surgery, at week 2, 4, 6, 8, 10, and 10 after surgery. Pathological changes of renal tissues were observed under light microscope. Morphological changes of mitochondria in renal tubular epithelial cells were observed under transmission electron microscope. Activities of antioxidant enzymes including reduced glutathione (GSH), manganese superoxide dismutase (MnSOD), and malondialdehyde (MDA) in fresh renal tissue homogenate were detected. Mitochondria of renal tissues were extracted to detect levels of mitochondrial membrane potential and changes of reactive oxygen species (ROS). And expressions of cytochrome-C (Cyto-C) and prohibitin in both mitochondria and cytoplasm of the renal cortex were also measured by Western blot.

RESULTS(1) Compared with the sham-operation group, body weight was significantly decreased at week 2 (P <0. 01), but blood pressure increased at week 4 (P <0. 05) in the model group. Compared with the model group, body weight was significantly increased at week 12 (P <0. 01), but blood pressure decreased at week 8 (P < 0. 01) in the treatment group. (2) Compared with the sham-operation group, 24 h proteinuria, urinary NAG, blood SCr and BUN significantly increased in the model group (all P <0. 01). Compared with the model group, blood and urinary biochemical indices all significantly decreased in the treatment group (all P <0. 01). (3) Results of pathological renal scoring: Glomerular sclerosis index, scoring for tubulointerstitial fibrosis, degree of tubulointerstitial inflammatory infiltration were all obviously higher in the model group than in the sham-operation group (all P <0. 01). All the aforesaid indices were more obviously improved in the treatment group than in the model group (all P <0. 01). (4) Compared with the sham-operation group, activities of MnSOD and GSH-Px were significantly reduced, but MDA contents obviously increased in the renal cortex of the model group (all P <0. 01). Compared with the model group, activities of MnSOD and GSH-Px obviously increased (P <0. 05, P <0. 01), but MDA contents obviously decreased in the renal cortex of the treatment group (P <0. 01). (5) Compared with the sham-operation group, the mitochondrial membrane potential significantly decreased, but ROS levels significantly increased in the model group (all P <0.01). Compared with the model group, mitochondrial transmembrane potential increased in the treatment group, thereby inhibiting the tendency of increased production of ROS (both P < 0. 01). (6) Results of Western blot showed that, compared with the sham-operation group, expression levels of mitochondrial Cyto-C and Prohibitin were significantly reduced in the renal cortex (P <0. 01), but significantly elevated in the cytoplasm of the model group (P <0. 01). Compared with the model group, each index was obviously improved in the treatment group with statistical difference (P <0. 05, P <0. 01).

CONCLUSIONCS powder had renal protection, and its mechanism might partially depend on in- hibition of oxidative stress and protection for mitochondria.

Acetylglucosaminidase ; metabolism ; Animals ; Blood Urea Nitrogen ; Cordyceps ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; Kidney Cortex ; Kidney Diseases ; Kidney Function Tests ; Male ; Malondialdehyde ; metabolism ; Mitochondria ; Nephrectomy ; Oxidative Stress ; drug effects ; Proteinuria ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

To assess the neurotoxic effects and redox responses of Aroclor 1254 (A1254) on perinatally exposed rat offspring, A1254 was administered by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Neurobehavioral development, antioxidant enzyme activities, lipid peroxidation (LPO), nitric oxide (NO), and NO synthase (NOS) levels were analyzed in the offspring. Neurobehavioral development analysis revealed delayed appearance of the righting reflex, negative geotaxis, and cliff drop test responses in A1254 exposed group. Developmental A1254 exposure also caused oxidative stress in the brain of PND 22 offspring via reductions in the activity of SOD and GSH-Px, and by promoting a rise in the levels of NO and NOS.
Aging ; metabolism ; Animals ; Cerebral Cortex ; drug effects ; enzymology ; metabolism ; Chlorodiphenyl (54% Chlorine) ; toxicity ; Female ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; enzymology ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; enzymology ; metabolism ; Mice ; Nervous System ; drug effects ; growth & development ; metabolism ; physiopathology ; Nervous System Diseases ; chemically induced ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the effect of Chinese herbs for stasis removing and collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis in the renal cortex of diabetic nephropathy rats.

METHODSTotally 89 male Sprague-Dawley rats were randomly divided into the blank control group (C group, n=22), the high-glucose high-fat control group (H group, n=10), and the streptozotocin (STZ)-injecting group (n=57). The diabetes rat model (n=50) was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ, which were further divided into the model group (M group, n=24), the irbesartan group (I group, n=13), and the CHSRCD (Z group, n=13). Rats in I and Z groups were intragastrically fed with suspension of irbesartan and CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated to rats in the rest groups. Blood glucose and 24 h urine protein quantitation were tested at four time points. And the mRNA expression of ACE2 and Mas at various time points was detected by Real-time PCR, immunohistochemical assay, and Western blot. Quantitative analyses of ACE2 and Mas protein expression were performed at the end of week 16.

RESULTSCompared with the C group, blood glucose increased in the H and M groups (P < 0.01). It was higher in the H group (P < 0. 01). 24 h urine protein quantitation at different time points increased in the M group, and it was higher than that in the H group (P < 0.05). Compared with the M group, 24 h urine protein quantitation decreased at the end of week 8 in the I group, and at the end of week 8 and 16 in the Z group (P < 0.05). It was lower in the Z group than in the I group at the end of week 16 (P < 0.05). Compared with the C and H groups, the expression of ACE2 mRNA in the renal cortex was lower in the M group at the end of week 16 (P < 0.01). Compared with the M group, it was higher in the Z group (P < 0. 01). There was no statistical difference in the expressions of Mas mRNA at the end of week 16 between the C group and the M group (P > 0.05). It was lower in the M group than in the H group (P < 0.05). It was higher in the Z group than in the M group (P < 0.05), and higher than in the I group (P < 0.05). The expression of ACE2 and Mas protein in the M group decreased as time went by. The expression quantitation of ACE2 and Mas protein at the end of week 16 was lower in the M group than in the C group (P < 0.05). Compared with the M group, ACE2 expression of the Z group and Mas of the I and Z groups increased more significantly (P < 0. 05).

CONCLUSIONCHSRCD could play a role in renal protection for diabetic nephropathy rats by up-regulating the mRNA and protein expression of ACE2 and Mas, promoting the ACE2-Ang-(1-7)-Mas axis, and lowering urinary protein.

Angiotensin I ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney Cortex ; metabolism ; Male ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism

OBJECTIVETo study the protective effect of panax notoginseng saponins (PNS) against apoptosis of the superficial cells of rat renal cortex following femoral fracture in rats.

METHODSNinety Wistar rats were randomized into 3 groups, namely the fracture group (n=36), fracture with PNS treatment group (n=36), and normal control group (n=18). At 1, 6, 12, 24, 36, and 48 h after femoral fracture, 6 rats from first two groups and 3 from the control group were sacrificed to observe renal pathologies with HE-staining. Immunohistochemistry and in situ hybridization were used to detect Bcl-2 and Bax expression, and TUNEL staining was employed to detect the distribution of apoptotic cells.

RESULTSIn the fracture group, the renal cortex showed telangiectasia and granular degeneration of proximal tubule, which were lessened in the PNS treatment group. Compared with the control group, the fracture group showed significantly increased Bcl-2 and Bcl-2 mRNA expressions in the renal cortex at 1-12 h (P<0.01) and increased Bax protein expression at 12-36 h (P<0.01) with increased Bax mRNA expression at 24-48 h (P<0.01). In PNS treatment group, Bcl-2 protein expression at 1 h and Bcl-2 mRNA expression at 12-48 h were significantly higher (P<0.01), but Bax protein and mRNA expressions at 24-48 h were significantly lower (P<0.01) than those in the fracture group.

CONCLUSIONFemoral fracture obviously affects Bcl-2 and Bax protein and mRNA expressions in the superficial cells of the renal cortex, PNS can suppress the cell apoptosis by down-regulating Bax expression and up-regulating Bcl-2 expression.

Animals ; Apoptosis ; drug effects ; Femoral Fractures ; pathology ; Kidney Cortex ; metabolism ; pathology ; Male ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Saponins ; isolation & purification ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo investigate the expression of C-type natriuretic peptides (CNP) and natriuretic peptide receptor-B (NPR-B) receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe (TLR).

METHODSSixty male SD rats were divided into 3 groups: the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin (STZ)-induced diabetic rats were treated with TLR (1.0 g·kg(-1)·d(-1)) for 4 and 12 weeks, respectively. (1) The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. (2) CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction (PCR) on rats renal cortex. (3) Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay (ELISA). (4) Pathological evaluation and NPR-B immunostaining for renal tissue were also performed.

RESULTS(1) CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. (2) Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. (3) Renal lesions like glomerular volume increased are observed mostly in the relative early stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement.

CONCLUSIONCNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.

Animals ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; genetics ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Gene Expression Regulation ; drug effects ; Hematuria ; complications ; genetics ; pathology ; Immunohistochemistry ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Cortex ; drug effects ; metabolism ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Male ; Natriuretic Peptide, C-Type ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; genetics ; metabolism ; Staining and Labeling ; Streptozocin

OBJECTIVETo investigate the antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction (, MDBD) on adraimycin-induced nephropathy in rats.

METHODSThirty-two male Sprague Dawley albino rats were randomly divided into 4 groups: the control, model, and two treatment groups, with 8 in each group. Nephropathy was induced in the latter 3 groups by intravenous injection of adriamycin. Rats in the two treatment groups received intragastric administration of benazepri (a positive control) or MDBD, which is composed of extracts of Radix Angelicae sinensis, Astragalus membranaceus (Fisch.) Bge and Rhizoma chuanxiong. Serum albumin, blood lipids, 24-h urine protein and urine N-acetyl-b-D-glucosaminidase (NAG) were measured every 2 weeks. The ratio of kidney to body weight was measured. The expressions of extracellular matrix proteins in the renal cortex, including colleagen IV (Col-IV) and fibronectin (FN), were examined by immunohistochemistry, and the transcription of genes encoding transforming growth factor β1 (TGF-β1), the tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 9 (MMP-9) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) at the end of the 8-week treatment.

RESULTSCompared with the untreated rats in the model group, MDBD significantly increased serum albumin, lowered the blood lipids and decreased the ratio of kidney to body weight. MDBD significantly reduced the excretion levels of urinary protein and NAG as well as the accumulation of extracellular matrix (ECM), including Col-IV and FN, in the renal cortex. Further, MDBD decreased TIMP-1 and TGF-β1 gene expressions and increased MMP-9 gene expression in the kidney.

CONCLUSIONSMDBD was effective in treating the rat model of nephropathy. The clinical benefit was associated with reduction of renal fibrosis. The antifibrotic effect of MDBD may be mediated through the regulation of TIMP-1, MMP and TGF-β1 gene expressions.

Acetylglucosaminidase ; urine ; Animals ; Body Weight ; drug effects ; Collagen Type IV ; metabolism ; Doxorubicin ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibronectins ; metabolism ; Fibrosis ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Kidney Cortex ; drug effects ; enzymology ; pathology ; physiopathology ; Kidney Diseases ; blood ; drug therapy ; physiopathology ; urine ; Kidney Function Tests ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triglycerides ; blood

OBJECTIVETo study the effect of Yanggan Yishui Granule (YGYSG) on 12-week-old spontaneously hypertensive rats (SHR) on plasma angiotensin II (Ang II), transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF) content and renal cortical Ang II, TGF-beta1, CTGF mRNA expressions, and to further explore the mechanism of YGYSG in the kidney protection.

METHODSForty 12-week-old male SHR were randomized into the model group, the Bella Plymouth group (at the daily dose of 1.8 mg/kg), the YGYSG low dose group (at the daily dose of 5.4 g/kg), and the YGYSG high dose group (at the daily dose of 27 g/kg), 10 in each group. Another ten Wistar-Kyoto (WKY) rats were included as the control group. Equal volume of normal saline was given to SHR by gastrogavage in the model group and the normal control group, once a day for six weeks. The plasma Ang II, TGF-beta1 and CTGF concentrations, and the renal cortical Ang II, TGF-beta1, CTGF mRNA expressions were measured in each group.

RESULTSBella Plymouth was superior to YGYSG in reducing plasma Ang II, TGF-beta1 and CTGF, while the high and low dose YGYSG showed no significant difference (P>0.05). In reducing plasma Ang II, TGF-beta1 and CTGF mRNA expressions, low doses YGYSG was similar to the role of Bella Plymouth, and the role of high dose YGYSG was superior to low dose YGYSG and Bella Plymouth.

CONCLUSIONYGYSG played a role in kidney protection mainly through reducing the Ang II , TGF-beta1 and CTGF expressions of kidney.

Angiotensin II ; blood ; metabolism ; Animals ; Connective Tissue Growth Factor ; blood ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertension ; drug therapy ; metabolism ; pathology ; Kidney Cortex ; metabolism ; pathology ; Male ; Phytotherapy ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Transforming Growth Factor beta1 ; blood ; metabolism

OBJECTIVETo investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats.

METHODSUninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked.

RESULTSCompared with those in normal control group, the numbers of apoptosis and the expression of GRP78, Caspase-12 in glomerular and tubular cells were much higher in the diabetic kidneys at 8 weeks. There was no significant difference between group A and group B.

CONCLUSIONActivation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.

Animals ; Apoptosis ; Caspase 12 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; pathology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Kidney Cortex ; metabolism ; pathology ; Male ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Wistar

BACKGROUNDLong-term use of steroid with large dosage might cause many adverse effects in kidney transplant patients; reducing steroid dosage to a low level for maintenance is helpful in avoiding the side-effects, but meanwhile, acute rejection may rise to be a main concern. The present research monitored the immune function changes and the incidence of acute rejection and infection after rapid steroid reduction to investigate the safety of this strategy.

METHODSA prospective trial was conducted, using tacrolimus and mycophenolate mofetil as the basic immunosuppressive regimen, in addition to antibody induction with basiliximab. Corticosteroid dosage was rapidly reduced to 10 mg/d seven days post-transplantation in the experimental group, and the standard corticosteroid therapy was employed in the control group. Patient immunity was monitored by the Immune Cell Function Assay pre- and two weeks post-transplantation. The incidence of acute rejection and infection were compared between the experimental and control group.

RESULTSComparison of intracellular adenosine triphosphate (iATP) values detected two weeks post-transplantation for the control group ((324 ± 45) ng/ml) and the experimental group ((345 ± 91) ng/ml) did not reveal a significant difference (P > 0.05). The incidence of acute rejection was analogous between groups (P > 0.05), while an increased incidence of infection was observed in the control group (53% (n = 16)) versus the experimental group (22% (n = 6), P < 0.05). Overall, recipients in the control group had longer and more recurrent infections than those in the experimental group (P < 0.05). Patients in the control group had a lower immune response ((235 ± 35) ng/ml) than those in the experimental group ((286 ± 16) ng/ml) when infection occurred (P < 0.05).

CONCLUSIONRapid reduction of steroid early after kidney transplantation does not lead to a significant rise in patient immunity. It is a safe and effective therapy for kidney transplant patients.

Adolescent ; Adrenal Cortex Hormones ; metabolism ; Adult ; Antibodies, Monoclonal ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Prospective Studies ; Recombinant Fusion Proteins ; therapeutic use ; Young Adult

The aim of this study is to investigate the effects and mechanism of extract of Apocynum venetum (AV) on kidneys of streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in rats by intraperitoneal injection of streptozotocin (STZ). The indexes of the blood glucose, renal function and oxidative stress were observed. The DM rats were administrated with the AV for 8 weeks, the above-mentioned indexes were detected. The blood glucose level, BUN, 24 h urine protein excretion, urine volume, renal index, renal cortex's MDA level in model groups all increased significantly. Renal cortex's SOD and GSH activities decreased significantly compared with the normal control group (P < 0.05). The above-mentioned indexes were significantly improved by the AV treatment (P < 0.05). AV have protective effects on renal function of kidneys of streptozotocin-induced diabetic rats, and maybe via inhibition of the renal oxidative stress.
Animals ; Apocynum ; chemistry ; Blood Glucose ; metabolism ; Blood Urea Nitrogen ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fructosamine ; blood ; Glutathione Peroxidase ; metabolism ; Kidney ; physiopathology ; Kidney Cortex ; pathology ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism