In order to investigate the effect of ligustrazine (Lig) i.p. on peritoneal permeability in peritoneal dialysis and its side effects, creatinine was given intravenously and continuously to maintain the high plasma creatinine level. All the rabbits were divided into three groups: normal control group (group A), group B treated with 0.12% Lig and group C treated with 0.24% Lig. The peritoneal dialysis of all rabbits lasted 2 h. The plasma and dialysate levels of glucose, protein and creatinine were observed immediate, 30 min, 60 min, 90 min, 120 min after dialysis. Creastinine dialysate/plasma ratio (D/P), protein D/P ratio, glucose D/Do at different time points after dialysis and creatinine mass transfer area coefficient (MTAC) at 120 min were calculated. The structures of peritoneum were observed under optical microscope and electron microscope after continuously intraperitoneal injection of Lig for 14 days. The results showed that the 90-min and 120-min creatinine D/P ratios in the group C were higher than in the group A. The 120-min creatinine MATC in the group C was higher than in the group A. The rabbits treated with Lig did not show significant structure changes of peritoneum and signs of peritoneal irritation. It was suggested that Lig could increase mass transfer ability of peritoneum without significant side effects.
Animals ; Biological Transport ; Cell Membrane Permeability ; Creatinine ; blood ; Dialysis Solutions ; chemistry ; Peritoneal Dialysis ; methods ; Peritoneum ; metabolism ; Pyrazines ; pharmacokinetics ; pharmacology ; Rabbits

In order to investigate the effect of ligustrazine (Lig) i.p. on peritoneal permeability in peritoneal dialysis and its side effects, creatinine was given intravenously and continuously to maintain the high plasma creatinine level. All the rabbits were divided into three groups: normal control group (group A), group B treated with 0.12% Lig and group C treated with 0.24% Lig. The peritoneal dialysis of all rabbits lasted 2 h. The plasma and dialysate levels of glucose, protein and creatinine were observed immediate, 30 min, 60 min, 90 min, 120 min after dialysis. Creastinine dialysate/plasma ratio (D/P), protein D/P ratio, glucose D/Do at different time points after dialysis and creatinine mass transfer area coefficient (MTAC) at 120 min were calculated. The structures of peritoneum were observed under optical microscope and electron microscope after continuously intraperitoneal injection of Lig for 14 days. The results showed that the 90-min and 120-min creatinine D/P ratios in the group C were higher than in the group A. The 120-min creatinine MATC in the group C was higher than in the group A. The rabbits treated with Lig did not show significant structure changes of peritoneum and signs of peritoneal irritation. It was suggested that Lig could increase mass transfer ability of peritoneum without significant side effects.
Biological Transport ; Cell Membrane Permeability ; Creatinine/blood ; Dialysis Solutions/chemistry ; Peritoneal Dialysis/*methods ; Peritoneum/*metabolism ; Pyrazines/*pharmacokinetics ; Pyrazines/pharmacology

BACKGROUND: Considering that dialysate calcium concentration is potentially a main determinant of the serum ionized calcium level and vasoconstriction is associated with the blood calcium concentration, we conducted a study to evaluate the interdialytic effects of treatment with a low calcium dialysate (LdCa, 1.25 mmol/L) on the changes in arterial compliance (AC), blood pressure (BP), biochemical parameters and vasoactive substances. METHODS: Eight hemodialysis (HD) patients (mean age: 46.8 +/- 13.7 years, 4 men and 4 women) were included in the study. AC, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), serum ionized Ca, intact-PTH, serum nitric oxide and aldosterone were compared after 10 sessions of treatment with LdCa. Right carotid artery diameter was measured 3 times using a real time B-mode ultrasound imager (Hewlett-Packard Sonos 2000 (R) ) and AC was calculated using the Hayoz method. RESULTS: 1) AC was recorded as 0.140 (0.080-0.170) mm2/kPa at the baseline (1.75 mmol/L calcium dialysate), 0.170 (0.050-0.290) mm2/kPa after LdCa treatment (p< 0.05 versus baseline), and 0.140 (0.070-0.250) mm2/kPa following the HdCa treatment (p< 0.05 versus LdCa data). 2) MAP and PP were calculated at 114.12 +/- 10.56 mmHg and 63.50 +/- 10.87 mmHg at the baseline; 98.37 +/- 15.14 mmHg and 56.50 +/- 5.95 mmHg after LdCa treatment (p< 0.05 versus baseline) ; and 115.75 +/- 9.64 mmHg and 62.00 +/- 15.71 mmHg following HdCa treatment (p< 0.05 versus LdCa data). 3) Serum ionized Ca and intact-PTH were measured at 4.66 +/- 0.40 mg/dL and 25.08 +/- 16.44 pg/mL at the baseline; 4.45 +/- 0.28 mg/dL and 90.71 +/- 27.03 pg/mL after LdCa treatment (p< 0.05 versus baseline) ; and 4.65 +/- 0.43 mg/dL and 24.08 +/- 15.44 pg/mL following HdCa treatment (p< 0.05 versus LdCa data). 4) Serum aldosterone concentration was 300.8 (65.5-836.1) pg/mL at the baseline, and 220.2 (42.8-527.9) pg/mL after LdCa treatment (p< 0.05). CONCLUSION: There were favorable changes in AC, BP, biochemical parameters after treatment with LdCa. These changes may be associated with the reduction in serum ionized calcium and decreased serum aldosterone concentration.
Adult ; Arteries/drug effects ; Blood Pressure/*drug effects ; Calcium/*pharmacology ; Compliance/drug effects ; Cross-Over Studies ; Dialysis Solutions/*pharmacology ; Female ; Human ; Kidney Failure, Chronic/*physiopathology/therapy ; Male ; Middle Aged ; *Renal Dialysis ; Support, Non-U.S. Gov't

OBJECTIVE: To investigate the expression of galectin-1 with the stimulation of peritoneal dialysis solution (PDS) and its role in the epithelial-to-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs). METHODS: HPMCs were stimulated with PDS containing different concentrations of high glucose (1.5%, 2.5%, and 4.25%). After 24 h, mRNA and protein expressions of galectin-1,vimentin, and zo-1 were analyzed with real-time PCR and Western blot, respectively. Liposome transfected siRNA technique was used to knock down the expression of galectin-1 and the effect of galectin-1 siRNA on the EMT of HPMCs was also observed under 4.25% PDS condition. RESULTS: mRNA expression of galectin-1 in HPMCs increased in PDS groups, especially in group with 4.25% PDS (P<0.05). Protein expression of galectin-1 in HPMCs significantly increased in PDS groups with a dose dependent manner (P<0.05).Expression of vimentin in HPMCs significantly increased in PDS groups, especially in groups of 2.5% PDS and 4.25% PDS (P<0.05), but zo-1 expression markedly decreased (P<0.05). The expression of galectin-1 correlated positively with vimentin (P<0.05) but negatively with zo-1 (P<0.05). Expression of vimentin in groups of 4.25% PDS was markedly inhibited (P<0.05) by galectin-1 siRNA, whereas zo-1 expression was significantly increased (P<0.05). CONCLUSION Galectin-1 can mediate high glucose PDS-induced EMT in HPMCs and may be a new target for the prevention and treatment of peritoneal fibrosis.
Cells, Cultured ; Dialysis Solutions ; pharmacology ; Epithelial Cells ; cytology ; Epithelial-Mesenchymal Transition ; drug effects ; Galectin 1 ; genetics ; metabolism ; Glucose ; pharmacology ; Humans ; Peritoneal Dialysis ; adverse effects ; Peritoneal Fibrosis ; etiology ; Peritoneum ; cytology ; RNA, Messenger ; genetics ; metabolism

Cell Line ; Dialysis Solutions ; adverse effects ; Epithelial Cells ; metabolism ; Fibrosis ; Humans ; Peritoneal Dialysis, Continuous Ambulatory ; adverse effects ; Peritoneum ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; analysis ; RNA, Small Interfering ; pharmacology ; Transforming Growth Factor beta ; antagonists & inhibitors ; genetics ; Transforming Growth Factor beta1

OBJECTIVETo investigate the effects of peritoneal dialysis solution (PDS) on proliferation and apoptosis of rat peritoneal mesothelial cells (RPMCs).

METHODSThe proliferation of RPMCs treated with PDS containing glucose of different concentrations for different times in vitro were examined by MTT colorimeric assay. The cell cycles and cell apoptosis rate were determined by flow cytometry.

RESULTSAfter PDS treatment for 1 h, the cell proliferation inhibition rate, percentage of cells at G(0)/G(1) stage and early cell apoptosis rate increased, and such increment was more manifest with higher glucose concentration in PDS and longer treatment time of the cells. After treatment with PDS containing 4.25% glucose for 3 h, the proliferation inhibition rate of the RPMCs reached 44.12%, the percentage of cells at the G(0)/G(1) stage amounted to 71.95% and the early apoptosis rate reached 23.59%, which was several times higher than that of the negative control and 1.5% glucose/PDS groups, and also higher than that of 4.25% mannitol/PDS groups.

CONCLUSIONPDS containing high-concentration glucose can induce significant apoptosis and inhibit the proliferation of RPMCs in vitro.

Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dialysis Solutions ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; Male ; Peritoneal Dialysis ; Peritoneum ; cytology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of peritoneal dialysis solution (PDS) on apoptosis and intracellular free calcium([Ca(2+)]i), cell surface ICAM-1 expression of rat peritoneal mesothelial cells (RPMCs).

METHODSThe RPMCs apoptosis rate were determined by flow cytometry. [Ca(2+)]i in the cells were monitered the fluorescence at 528 nm by confocus laser microscopy. Cell surface ICAM-1 expression were detected by flow cytometry.

RESULTAfter PDS treatment for 1 h, the RPMCs apoptosis rate were increased. Such increase was more manifest with higher glucose concentration in PDS and longer treatment time of the cells. At the same times, after 3 hours, ICAM-1 expressions of the PDS containing glucose and mannitol are all increased. With the increase of glucose concentrations, the descend of [Ca(2+)]i levels were aggravated.

CONCLUSIONPDS containing high- concentration glucose can induce significant apoptosis of RPMCs in vitro. This may be related with the enhanced level of ICAM-1 expressions and the decreased level of [Ca(2+)]i. Which may due to the occurrence of peritoneal fibrosis and ultrafiltrate failure in patients suffering long term peritoneal dialysis.

Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Dialysis Solutions ; pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Glucose ; pharmacology ; Intercellular Adhesion Molecule-1 ; metabolism ; Intracellular Space ; drug effects ; metabolism ; Male ; Peritoneal Cavity ; cytology ; Peritoneal Dialysis ; Rats ; Rats, Sprague-Dawley

To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis.Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs., compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (all<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all<0.05)., the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF were significantly increased in HPECs of peritoneal dialysis group (all<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF (all<0.05).High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.
Animals ; Cells, Cultured ; Connective Tissue Growth Factor ; analysis ; drug effects ; Dialysis Solutions ; adverse effects ; chemistry ; pharmacology ; Gene Expression Regulation ; drug effects ; Glucose ; adverse effects ; pharmacology ; Glucose Transporter Type 1 ; analysis ; drug effects ; physiology ; Hemodiafiltration ; adverse effects ; methods ; Humans ; Male ; Peritoneal Dialysis ; adverse effects ; methods ; Peritoneal Fibrosis ; chemically induced ; genetics ; physiopathology ; Peritoneum ; chemistry ; drug effects ; pathology ; Phloretin ; Phlorhizin ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Sodium-Glucose Transporter 1 ; analysis ; drug effects ; physiology ; Transforming Growth Factor beta1 ; analysis ; drug effects ; Uremia ; chemically induced