Sorafenib ameliorates renal fibrosis through inhibition of TGF-β/Smad pathway / 西安交通大学学报(医学版)

Objective To investigate the effect of sorafenib in ameliorating renal fibrosis and its possible mechanisms.Methods Rats were subjected to unilateral ureteral obstruction (UUO ) and intragastrically administered sorafenib.NRK-52E cells were treated with transforming growth factor-β1 (TGF-β1)and sorafenib. HE staining was used to visualize renal fibrosis.α-SMA and E-cadherin expressions in kidney tissue and NRK-52E cells were performed using immunofluorescence.The cell cycle of NRK-52E cells was determined by flow cytometry analysis.Smad3 and p-Smad3 protein expressions in NRK-52E cells were detected by Western blot analysis. Results HE staining showed that kidney interstitial fibrosis,tubular atrophy,and inflammatory cell infiltration in the sorafenib-treated UUO groups were significantly decreased compared with the vehicle-treated UUO group (P<0.05).Compared with those in UUO and TGF-β-stimulated NRK-52E groups,the expression of a-SMA decreased but E-cadherin expression increased in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (P<0.05).After 24 h stimulation with TGF-β1 5 ng/mL,the number of cell cycles arrested in G0/G1 phase was significantly increased and the number of cells that entered G2 ,S phase decreased (P<0 .0 5 ).Compared with that in TGF-β-stimulated NRK-52E groups, p-Smad3 decreased in the sorafenib-treated groups (P<0.05). Conclusion Our results suggest that sorafenib may be useful for the treatment of renal fibrosis through suppressing TGF-β/Smad3 signaling.

Solute clearance effect of citrate anticoagulation hemodialysate for hemodialysis in patients with high risk of bleeding / 药物分析学报

Objective To study the solute clearance effect of the new concentrated anticoagulation hemodiaiysate of citrate for hemodialysis in patients with high risk of bleeding. Methods Forty-two kidney failure patients with high risk of bleeding were divided into two groups (Group A and Group B) according to their hemodialysis manners. Patients in Group A were hemodialyzed with bicarbonate hemodialysate with low-molecular-weight heparin (dalteparin) anticoognlation and those in Group B with the new citrate antieoagnlation hemodialysate prepared in our hospital without any other anticoagulant. Blood urea nitrogen (BUN) and creatinine (Cr) concentrations were measured before and after dialysis, and Kt/V and urea reduction rate (URR) were calculated. In addition, activated clotting time (ACT) and ionized calcium (iCa2+) concentration were also measured at the arterial and venous ends. Results ACT was extended and iCa2+ concentration decreased significantly at the venous end compared with those at the arterial end in Group B (P<0.01). BUN and Cr concentrations were markedly decreased after dialysis compared with those before dialysis in both groups (P<0.01), and no significant difference in solute clearance effect, as indicated by Kt/V and URR, was observed between Group A and Group B (P>0.05). Conclusion The solute clearance effect of the new concentrated anticoagnlation hemodialysate of citrate is excellent during hemodiaiysis in kidney failure patients with high risk of bleeding.

Effect of all-trans retinoic acid on the excretion of urine TGF ?_1 and glomerular lesion of diabetic rat / 西安交通大学学报(医学版)

Objective To investigate the effect of all-trans retinoic acid(atRA) on the urinary TGF?_1 excretion and glomerular lesion of diabetic rats at early stage.Methods SD rats were randomly assigned into 3 groups: atRA treated group,diabetic control group and normal control group.Streptozotocin(STZ)-induced early diabetic male SD rat were used.The atRA treated group were treated with daily subcutaneous injections atRA of 10mg/kg for 7 days(n=6),and then the excretion of urinary protein and TGF?_1 and NO level of plasma,urine and renal tissue were measured,and pathological changes of their kidneys were observed.Results The diabetic control rats showed increased urinary excretion of protein and TGF?_1 and NO level of plasma,urine and renal tissue and deposit of glomerular matrix,while atRA prevented these changes.Conclusion AtRA can prevent the development of diabetic nephropathy,which is relevant with the inhibition of secretion of TGF?_1 and NO.

Study on solute clearance effect of the new anticoagulation hemodialysate of citrate / 中国实用内科杂志

Objective To study the solute clearance effect of t he new concentrated anticoagulation hemodialysate of citrate for hemodialysis in patients with high risk of bleeding.Methods During the period of 2002-06~2003-12,42 patients with h igh risk of bleeding were divided into two groups according to hemodialysis mann ers.Group Ⅱ were hemodialyzed with new citrate anticoagulation hemodialysate wi thout any other anticoagulant and group Ⅰ were hemodialyzed with bicarbonate he modialysate with dalteparin anticoagulation.The BUN and Cr levels were determine d before and after dialysis and Kt/V and URR were calculated.In addition,ACT and iCa 2+ were also measured at the artery and venous end.Results ACT was extended and iCa 2+ decreased significantl y at the venous end compared with that at the artery end in group Ⅱ (P0.05).Conclusion The solute clearance effect of the new concentrated anticoagulation hemodialysate of citrate for hemodialysis in patients with high risk of bleeding is excellent.

Intervention of renal connective tissue growth factor expression and renal fibrosis by Benazepril:an experimental study in unilateral ureteral obstruction rats / 西安交通大学学报(医学版)

Objective To study the effect of Benazepril on the renal connective tissue growth factor(CTGF) expression and interstitial fibrosis in unilateral ureteral obstruction(UUO) rats and to illuminate the possible mechanisms.Methods 24 Sprague-Dawley rats were randomly divided into Sham-operated,control and Benazepril groups.From the day before operation,the rats were under intragastric administration of Benazepril 10mg/(kg?d) in Benazepril group,and sodium chloride in tales doses in Sham and control groups.On the 14~(th) day after operation,the obstructed kidney was taken out to be measured by HE,Masson,and immunohistochemistry staining for TGF-?_1,CTGF,?-SMA and ColⅢ.Results The score of renal interstitial lesion and fibrosis index in Benazenpril were significantly lower than those in the control group(P

Effect of all-trans-retinoic acid on tubulointerstitial macrophage infiltration in rats with renal tubulointerstitial fibrosis / 西安交通大学学报(医学版)

Objective To investigate the effect of at-RA in macrophage accumulation in tubulointerstitium of rats with renal tubulointerstitial fibrosis.Methods Unilateral ureteral obstructive(UUO) rat animal models were used for the study.40 SD rats were randomly divided into 5 groups: sham group,UUO group,benazepril group,low-dose at-RA groups and high-dose at-RA groups.The rats were under intragastric administration by benazepril(10mg/(kg?d)) in benazepril group,and by(at-RA)(10mg/(kg?d)) in low-dose at-RA group and 20mg/(kg?d) in high-dose at-RA group and by sodium chloride in tales doses in sham group and UUO group from the day before the operation to 14 day after operation.Immunohistochemistry staining of CD68 and Col Ⅲ was used to define the macrophage accumulation and expression of interstitial Col Ⅲ.The degree of tubulointerstitial damage was scored by HE and Masson staining.Results Tubulointerstitial macrophage infiltration were all significantly reduced by(at-RA) or benazepril treatment.They also improved the histological changes of UUO rats and inhibited interstitial colⅢ deposition.Conclusion Reduction of interstitial macrophage infiltration may be an important event by which(at-RA) or benazepril prevents renal injury caused by UUO.

The protective function of oxymatrine on renal interstitial fibrosis in rats / 西安交通大学学报(医学版)

Objective To investigate the protective function of oxymatrine on the renal intestitial fibrosis in rats.Methods Forty male Sprague Dawley rats were randomly divided into 5 groups: sham group,model group,Lotensin group,large-dose oxymatrine group,and small-dose oxymatrine group.The models were established by unilateral ureteral obstruction(UUO) of the left side.On the 14~(th) day after operation,the obstructed kidney was taken out.Then,HE,Massion,and immunohistochemistry staining of transforming growth factor-?_(1)(TGF-?_(1)),(?-smooth) muscle acting(?-SMA) and collagen Ⅲ were conducted.After that,semiquantitative analysis was performed.Results After oxymatrine,treatment,the expressions of ?-SMA,TGF-?_(1) and ColⅢ of the obstructed kidney in the treatment group were significantly lower than those in the model group(P0.05).Conclusion Oxymatrine may reduce the expression of cytokines such as TGF-?_(1),then the activation of cell producing ECM and then the sendimentation of ECM,thus preventing renal interstitial fibrosis.

AN APPRECIATION OF PITIUTARY FUNCTION TESTS FOR THE DIAGNOSIS OF DIABETES INSIPIDUS / 西安交通大学学报(医学版)

The pitiutary function tests in diabetes insipidus were compared by means of analyses of clinical data. It is considered that the water deprivation-ADH test is more reliable than the hypertonic saline test in differential diagnosis of complete diabetes insipidus from partial diabetes insipidus and central diabetes insipidus from nephrogenic diabetes insipidus. Some suggestions on the time of water deprivation test, the improvement of hypertonic saline solution test and diagnosis of partial nephrogenic diabetes insipidus were made in this paper.