The effect of TGF-β/ILK pathway in endothelial-mesenchymal transition induced by parathyroid hormone in human vascular endothelial cells / 重庆医学

Objective To investigate the molecular mechanism of endothelial-mesenchymal transition (EndMT) induced by uremic toxin,parathyroid hormone (PTH),in vascular endothelial cells.Methods PTH (1 × 10-8 mol/L) was used to induce EndMT in human aortic endothelial cells (HAECs).TGF-β signaling inhibitor,including SB431542 and pirfenidone (PFD),and integrin-linked kinase (ILK) inhibitor Cpd22 were used to investigate the potential mechanism of EndMT induced by PTH in HAECs.Then the vascular endothelial cell markers VE-cadherin and CD31,and the mesenchymal marker α-SMA were detected by western blot.Results PTH reduced the expression levels of vascular endothelial cell marker CD31 and VE-cadherin (P＜0.05),while significantly increased the expression level of fiber cell marker α-SMA(P＜0.05).Furthermore,the TGF-βsignaling inhibitors (SB431542 and PFD) and ILK inhibitor (Cpd22) were able to partially reverse the EndMT induced by PTH in HAECs,which reversed the effect of PTH on reducing vascular endothelial cell marker expression and increasing fiber cell marker expression.Conclusion PTH could induce EndMT in HAECs via TGF-β/ILK pathway.

Selection of appropriate period and mode of blood purification for treatment of patients with severe acute pancreatitis / 中国中西医结合急救杂志

Objective To approach the selection of appropriate period and mode of blood purification for treatment of patients with severe acute pancreatitis(SAP)based on acute physiology and chronic health evaluationⅡ(APACHEⅡ)score. Methods The clinical data of 89 patients with SAP were retrospectively analyzed. They were assigned into two groups:the hemoperfusion(HP)and short continuous veno-venous hemodiafiltration(SCVVHDF) group(HP+SCVVHDF,49 cases)and the HP and hemodiafiltration(HDF)group(HP+HDF,40 cases). All the patients were evaluated by APACHEⅡscore. In the HP+HDF group,26 cases with APACHEⅡ0.05),while the APACHEⅡ score,PaO2/FiO2,CRP, SCr and ALT were improved more significantly in group C than those in group B(P<0.05 or P<0.01). The mortality rate of those SAP patients with APACHEⅡscore<15 was lower than those in cases with APACHEⅡscore 15-20〔6.82%(3/44)vs. 24.44%(11/45),P<0.05〕. Conclusions Blood purification is an effective measure to save patients with SAP. The APACHEⅡ score used to select the mode of blood purification in appropriate period for treatment of SAP has guiding significance. Currently the modes of blood purification have limited value and cannot cure all SAP patients.

Fibrosis of middle-small arteries and veins in early-stage uremic patients / 第三军医大学学报

Objective To explore the pathological changes of the middle-small arteries and veins of uremic patients in early stage.Methods Forty patients with chronic kidney disease at Ⅴ stage were randomly subjected in our study.Radial artery and cephalic vein about 0.5 to 1 cm in length were obtained by arteriovenous fistula operations.Cephalic veins from 4 trauma patients were taken as control group.Immunohistochemisty with anti-?-SMA(smooth muscle actin-alpha),BMP-2(bone morphology protein-2) and BMP-7(bone morphology protein-7) antibodies,alizarin Bordeaux staining,HE staining and Masson trichrome staining were carried out to investigate calcification and fibrosis.Results Compared with control group,the expressions of ?-SMA and BMP-2 were up-regulated obviously.Masson trichrome staining indicated fibrosis in the vein from uremic patients.Conclusion Fibrosis may be one of the early pathologic changes in the vein from uremic patients,suggesting the venous alterations may be related to cardiovascular disease of uremic patients.

Endothelial progenitor cells transplantation ameliorates the progression of progressive focal segmental glomerular sclerosis / 第三军医大学学报

Objective To investigate the therapeutic effect of endothelial progenitor cells(EPCs) in ameliorating rat progressive focal segmental glomerular sclerosis(FSGS) model induced by adriamycin.Methods Bone marrow mononuclear cells from male SD rats,after cultured by adherence method,were identified as EPCs.Female SD rats were divided into normal control group,adriamycin induced renal disease(ADR) group,EPCs transplantation group.ADR group and EPCs group underwent unilateral nephrectomy and received 5,3 mg/kg of adriamycin via tail vein 1 week and 2 weeks after operation,while the control group underwent sham operation and received 0.9% sodium chloride solution of equal volume.The whole body irradiation by 5 Gy X ray was done 1 week after the 2nd injection of adriamycin,then immediately 1?106 EPCs were transplanted via tail vein.The rats in control group and ADR group were only injected with 0.9% sodium chloride solution after whole body irradiation.The body weight and urine protein were measured before operation(0 week) and 4(1 week after EPCs transplantation),8,12 and 16 weeks after nephrectomy.Y chromatosome incorporation was detected with in situ hybridization at the 4th and 16th week.The histological and ultrastructural changes of kidney were evaluated at the 16th week.Results At the 4th and 16th weeks,Y chromatosome positive cells could be found incorporation in the area of glomerular and tubular epithelial cells.Since the 4th week,the weight of rats in both ADR group and EPC group became significantly less than that in control group and since the 8th week that in ADR group became less than that in EPC group(P

THE CHANGES OF MYOCARDIAL ULTRASTRUCTURE AND CELL MEMBRANE CHANNEL IN UREMIC RATS / 解放军医学杂志

The aim of this study was to explore the myocardial ultrastructure of experimental uremic rats and the effect of myocardiocyte succinate dehydrogenase(SDH) and free cytosolic calcium changes on membrane channel. By making a uremia model in rats, changes of SDH activation was observed by quantitative enzyme cytochemistry methods and membrane calcium channel was checked by laser scanning confocal microscopy. The results showed that with the uremia becoming heavier, myocardiocyte membrane was rolled and broken, myofibrils were swollen and broken. The quantity of mitochondria with SDH products significantly decreased, while activation of cell membrane calcium channel markedly increased and cytosolic calcium piled up. It is suggested that impaired myocardial membrane, decreased contents of mitochondrial function enzyme and cytosolic calcium overload are the pathophisiological basis leading to cardiac dysfunction in uremia.

Effect of benapril on atherogenesis and plaque rupture in rabbits / 第二军医大学学报

Objective: To examine the effect of Benapril on atherogenesis and the plaque rupture in rabbits.Methods: Thirty four healthy male New Zealand white rabbits were randomly divided into 4 groups.Group C (control group) was fed normal diet for 10 weeks,group HL fed 1% cholesterol diet,group B fed 1% cholesterol diet and Benapril 5 mg/d.Ten rabbits of plaque rupture group were fed 1% cholesterol diet for 10 weeks with atherosclerosis induced by left carotid iliac damage.Ten weeks after the initiation of the diet,an angioplasty was performed.After angioplasty,the surviving rabbits( n =10) were randomized to receive benapril(5 mg/d,each) supplementation in drinking(B group, n =4) or no treatment(untreated group, n =4). The levels of CEC were measured by morphometrical counts at different periods(the 5th week,the 10th week).Before and 5,10 weeks after experiment,fasting blood samples were collected for serum total cholesterol(TC),high density lipoprotein cholesterol(HDL C),low density lipoprotein cholesterol(LDL C),and triglyceride(TG) assay.The levels of plasma circulating endothelial cells(CEC) were measured by morphometrical counts and the levels of plasma von Willebrand factor(vWF) were determined by ELISA.After sacrificing the separated, entire aortas were stained with oil red O and then processed for histological examination;planimetry was done with a computer system.Endothelial cells were confined by the presence of Factor Ⅷ related antigen as the specific cell marker.Results: The serum TC,TG,LDL C increased progressively in group B and group HL,but the levels of vWF in group HL were significantly higher than that in group B on the 5th and 10th respetively( P

STUDY ON THE EFFECT OF BENAPRIL ON ATHEROGENESIS, CIRCULATING ENDOTHELIAL CELLS AND FACTOR vWF / 解放军医学杂志

To examine the effect of benapril on atherogenesis, circulating endothelial cells (CEC), and factor vWF. Twenty four healthy male New Zealand white rabbits were randomly divided into 3 groups. In group C (control group) the rabbits were fed normal rabbit diet for ten weeks, in group AS 1% cholesterol diet was fed, and in group B both 1% cholesterol diet and benapril 5mg/day were fed. Fasting blood samples were collected for the determination of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL c), low density lipoprotein cholesterol (LDL c), and triglyceride (TG) on day 0, 5 and 10 weeks after feeding. The levels of plasma CEC were measured by morphometrical count and the levels of plasma vWF were determined by ELISA. After the animals were sacrificed, aortas were obtained, and they were stained with oil red O. The tissue was sectioned for histological examination. Planimetry was performed with a computer system. Endothelial cells were identified by the presence of factor VIII related antigen, which was the specific marker for endothelial cells. The results showed that the levels of serum Tc, TG, and LDL c were increased progressively in group B and group AS, but the levels of vWF in group AS were significantly higher than that in group B at the 5 th and 10 th weeks respectively ( P