OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

OBJECTIVETo observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism.

METHODSThirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot.

RESULTSHE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01).

CONCLUSIONBHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.

Animals ; Blood Urea Nitrogen ; Bone Morphogenetic Protein 2 ; metabolism ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; pathology ; Kidney Failure, Chronic ; drug therapy ; metabolism ; Kidney Function Tests ; Kidney Tubules ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factors ; metabolism ; Vascular Calcification ; drug therapy

OBJECTIVETo observe the effect of Shenshuai Yingyang Capsule (SSYYJN) in ameliorating muscle atrophy in rats with chronic renal failure (CRF) and explore the role of Wnt7a-Akt/mTOR signal pathway in mediating this effect.

METHODSMale rats were randomly assigned to 5/6 nephrectomy group and sham-operated group, and the former group was further randomly divided into CRF model group, KA group, and SSYYJN group. The size of anterior tibia muscle was examined microscopically with HE staining. Protein synthesis in the soleus muscle was investigated by (14)C-phenylalanine experiment, and the expression of Wnt7a, frizzled-7, phospho-Akt, phospho-mTOR and GAPDH were detected with Western blotting.

RESULTSThe body weight, the wet and dry weight, cross-sectional area, and muscle protein synthesis of the anterior tibia muscles, and expressions of the proteins in the Wnt7a/Akt signaling pathway all increased significantly in SSYYJN and KA groups as compared with those in the model group.

CONCLUSIONSSYYJN can effectively improve muscle atrophy in the rat model of CRF possibly by reversing the reduction in the expressions of Wnt7a/Akt signaling pathway proteins in the skeletal muscles.

Animals ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Kidney Failure, Chronic ; complications ; Male ; Muscle Proteins ; biosynthesis ; Muscle, Skeletal ; drug effects ; Muscular Atrophy ; drug therapy ; Nephrectomy ; Proto-Oncogene Proteins ; metabolism ; Rats ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism ; Wnt Proteins ; metabolism

OBJECTIVETo observe the effect of compound Huang Gan in delaying chronic renal failure in rats after 5/6 nephrectomy and explore the possible mechanisms.

METHODSHigh-performance liquid chromatography was used to was used identify the components of compound Huang Gan extract. Rat models of 5/6 nephrectomy received a 12-week treatment with intragastric administration of Niaoduqing, Cozaar, or compound Huang Gan at low, moderate or high doses (n=10). After the treatments, the rats were sacrificed for detecting Scr, BUN, Ucr and 24h UPr , pathological examination of the renal tissues, and determination of FN, MCP-1, and ICAM-1 expression levels in the renal tissues using RT-PCR and immunohistochemistry.

RESULTSThe major chemical components of compound Huang Gan extract included glycyrrhizin (0.61%), paeonol (1.2%), aloe emodin (0.72%), rhein (0.85%), emodin (0.87%), chrysophanol (0.79%) and physcion (0.8%). Treatment with compound Huang Gan at low, moderate and high doses significantly reduced Scr, BUN, Ucr , Ccr and 24 h UPr levels (P(P<0.05), improved interstitial fibrosis and glomerulosclerosis, and reduced FN and ICAM-1 expressions (P(P<0.05) in rats following nephrectomy.

CONCLUSIONSCompound Huang Gan can improve the renal function and lessen glomerulosclerosis and renal interstitial fibrosis to delay the progression of chronic renal failure in rat models of 5/6 nephrectomy.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Fibronectins ; metabolism ; Fibrosis ; Intercellular Adhesion Molecule-1 ; metabolism ; Kidney ; pathology ; Kidney Failure, Chronic ; drug therapy ; Nephrectomy ; Rats

OBJECTIVETo investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats.

METHODSForty SPF SD rats were divided into sham group (n=10),model group (n=10), Jianpi Qinghua group (n=10) and losartan group (n=10). Rat chronic renal failure was induced by 5/6 nephrectomy (Platt method) in model, Jianpi Qinghua and losartan groups, and rats in sham group received sham operation. Jianpi Qinghua decoction (3.9 g 200 g(-1)) or losartan (3.3 g 200 g(-1)) daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days, respectively, Rats in sham and model groups were orally administered with saline of the same volume. The serum levels of creatinine and urea nitrogen were measured by biochemical method, the expression of MAPK p38 was detected by Western Blot,and renal pathological changes were observed with hematoxylin-eosin staining.

RESULTSCompared to model group,serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly (42.67 ± 5.98 or 40.90 ± 5.07 compared with 60.90 ± 9.54, both P<0.01), the expression of MAPK p38 was significantly down-regulated (0.555 ± 0.004 or 0.587 ± 0.045 compared with 0.930 ± 0.265,both P<0.01) and serum urea nitrogen was also decreased (8.56 ± 0.75 or 7.97 ± 0.86 compared with 8.62 ± 0.62,both P<0.05). The renal pathology in the model group presented glomerular mesangial proliferation,hyperplasia of glomenrulus mesangial cells and interstitial inflammation. Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups.

CONCLUSIONJianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure, which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.

Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; enzymology ; MAP Kinase Signaling System ; Male ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis.

METHODSSixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined.

RESULTSThe patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05).

CONCLUSIONSequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.

Adolescent ; Adult ; Aged ; Alprostadil ; therapeutic use ; Blood Urea Nitrogen ; Chronic Disease ; Creatinine ; blood ; Drug Therapy, Combination ; Epoprostenol ; analogs & derivatives ; therapeutic use ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Glomerular Filtration Rate ; Glomerulonephritis ; complications ; Humans ; Kidney Failure, Chronic ; blood ; drug therapy ; etiology ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Count ; Prothrombin Time ; Urological Agents ; therapeutic use ; Young Adult

The effective bioactivity compositions of uremic clearance granul (UCG) include isoflavonoids, emodin, astragaloside, paeoniflorin, salvianolic acid A, and so on. The effects of UCG treating chronic renal failure (CRF) in clinical pharmacodynamics mainly refer to improve renal function and the complications of CRF. The mechanisms involved in vivo basically include depressing transforming growth factor (TGF)-beta1 over-expression, lessening podocyte injury,inhibiting tubular epithelial myofibroblast transdifferentiation, ameliorating microinflammation status, retarding oxidative stress, and alleviating insulin resistance.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Kidney ; drug effects ; metabolism ; Kidney Failure, Chronic ; drug therapy ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo explore the mechanisms of Chinese herbal medicine Sanqi Oral Liquid, composed of Astragalus membranaceus and Panpax notoginseng, in alleviating renal injury by observing its effect on the expressions of CD4(+), CD8(+) and CD68(+) cells in 5/6 nephrectomized rats with chronic renal failure.

METHODSA total of 102 SD rats were randomly divided into six groups: three treatment groups were administrated with high, medium and low dosage of Sanqi Oral Liquid respectively by gavage; a normal group, a 5/6 nephrectomized model group, and a group treated with coated aldehyde oxygenstarch were used as controls. Following oral administration of Sanqi Oral Liquid for 12 weeks, the general condition and renal pathological changes were observed, and the renal function, platelet count (PLT) and the expressions of CD4(+), CD8(+) and CD68(+) cells were determined for each group.

RESULTSThere were proliferation of mesangial matrix, renaltubularnecrosis and obvious tubulointerstitial fibrosis in the model group, and they were much milder in the treatment groups. Compared with the model group, the amounts of blood urea nitrogen (BUN), serum creatinine (Scr) and PLT in the treatment groups decreased (P<0.05 for all); and in the group administrated of medium dosage of Sanqi Oral Liquid, the expression of CD4(+) cells was up-regulated and those of CD8(+) and CD68(+) cells were down-regulated (P<0.05 for all), leading to an increased ratio of CD4(+)/CD8(+)(P<0.01).

CONCLUSIONSanqi Oral Liquid has a significant effect on regulating lymphocyte subsets, reducing the infiltration of macrophages in renal tissues and alleviating tubulointerstitial fibrosis, and this may be one of mechanisms of Sanqi Oral Liquid in delaying the progression of chronic kidney diseases.

Administration, Oral ; Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Astragalus membranaceus ; chemistry ; CD4-Positive T-Lymphocytes ; drug effects ; pathology ; physiology ; CD8-Positive T-Lymphocytes ; drug effects ; pathology ; physiology ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Kidney Failure, Chronic ; drug therapy ; immunology ; pathology ; surgery ; Lymphocyte Count ; Male ; Nephrectomy ; Panax notoginseng ; chemistry ; Rats ; Rats, Sprague-Dawley ; Solutions

In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT) in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the optimal disease-free interval has not been specified for all subtypes of acute leukemia. Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis and low relapse rate compared to other types of leukemia. We here report KT after complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months after the achievement of CR. The patient's clinical course after KT was favorable, without allograft rejection or relapse of APL up to1 yr after KT. On the basis of our clinical experience, it is suggested that a long wait may not be necessary before KT in patients with ESRD and APL.
Adult ; Antineoplastic Agents/therapeutic use ; Arsenicals/therapeutic use ; Bone Marrow Cells/pathology ; Humans ; Kidney Failure, Chronic/*therapy/ultrasonography ; *Kidney Transplantation ; Leukemia, Promyelocytic, Acute/*diagnosis/drug therapy ; Male ; Oxides/therapeutic use ; Receptors, Retinoic Acid/genetics/metabolism ; Remission Induction

OBJECTIVETo observe the effects of Shenshuai II Recipe (SSR) on the fibrosis of remnant nephridial tissue and expressions of Ang II and nNOS in the chronic renal failure (CRF) rats induced by 5/6 ablation/infarction (A/I), and to preliminarily investigate its mechanism of action.

METHODSFifty-seven SD male rats were used to prepare the CRF rat model by means of 5/6 A/I. After modeling, they were randomly divided into the model group, the SSR group (2 mL SSR condensed decoction given by gastrogavage), and the Western medicine group (treated by 2 mL suspension of losartan potassium and fosinopril sodium given by gastrogavage), 15 rats in each group. Another 15 rats were recruited as the normal control group. Equal volume of pure water was given to rats in the normal control group and the model group. Relevant treatment was given to rats in each group once daily, for 60 successive days. The serum creatinine (SCr), blood urea nitrogen (BUN), and creatinine clearance rate (CCr) were detected. The expressions of angiotensin II (Ang II) and nervous system type nitric oxide synthase (nNOS) in the remnant renal cortex and the medulla were detected by Western blot. The pathomorphology of the nephridial tissue was observed.

RESULTSCompared with the normal control group, the levels of SCr and BUN increased (P<0.01) and the level of CCr decreased (P<0.01) in the model group, indicating a successful modeling. Compared with the same group before treatment, the levels of SCr and BUN decreased and the level of CCr increased in the SSR group and the Western medicine group (all P<0.01). Compared with the model group after treatment, the levels of SCr and BUN decreased, and the expression of Ang II in the medulla decreased in the SSR group and the Western medicine group (P<0.01, P<0.05). The levels of CCr and protein expressions of nNOS in the renal cortex and the medulla obviously increased in the SSR group and the Western medicine group (P<0.01, P<0.05). The pathology of the nephridial tissue showed that the pathological changes in the SSR group were obviously ameliorated, better than those of the model group.

CONCLUSIONSSSR could improve the renal function and relieve the renal interstitial fibrosis in the rats induced by 5/6 A/I. Its mechanism of action was possibly correlated with regulating the renal imbalanced Ang II and nNOS signal transduction pathway.

Angiotensin II ; metabolism ; Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney ; drug effects ; metabolism ; Kidney Failure, Chronic ; drug therapy ; metabolism ; pathology ; Male ; Nitric Oxide Synthase Type I ; metabolism ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects