A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n = 25), Uninephrectomy group (UPHT, n = 25) and Uninephrectomy+Daunorubicin group (DRB, n = 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Ang1 mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Ang1 protein had a positive correlation with the expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Ang1 expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.

To investigate the role and mechanisms of apoptosis and apoptosis signaling pathway in 5/6 nephrectomy rat model (SN(x)), the mRNA and protein levels of caspase-3, -8, -9 and apoptosis were detected by in situ end labeling (TUNEL), immunohistochemistry, RT-PCR, Western-blotting 1, 2, 4, 8, 12, 16, 26 and 40 weeks after 5/6 nephrectomy rat model was made respectively. The rats in the model group developed glomerular sclerosis and renal interstitial fibrosis. The number of the apoptototic cells in glomeruli, renal tubule and renal interstitium was remarkably higher in the model group than that in the control group (P < 0.05, P < 0.01). Changes of mRNA and protein level of caspase-3, -8, -9 had the same tendency and was up-regulated wavily in the rat model compared with the control group (P < 0.05). Peaks in model appeared on the 4th and the 40th week respectively. The growth amplitude of caspase-9 was remarkably higher than that of caspase-8. It is concluded that the development of 5/6 nephrectomy rat model was correlated with the apoptosis of glomeruli, renal tubule and renal interstitium. Both of death receptor and mitochondria signaling pathways are involved in the process and the latter might play a primary role.

Accumulating evidence suggests that the small G protein Rho and its downstream effector Rho kinase may play important roles in kidney biology. The present study examined the effects of a Rho-kinase inhibitor, fasudil, on daunorubicin-induced progressive glomerulosclerosis and explored the underlying mechanism by which fasudil ameliorates glomerulosclerosis. Thirty-six male SD rats were randomly allocated into sham-operation group (sham group, n=12), unilateral nephrectomy (UNX)+daunorubicin (DRB) group (model group, n=12), UNX+DRB+Fasudil group (treatment group, n=12). Two to four weeks after the establishment of the animal model, 6 rats in each group were taken randomly for the detection of 24-h urine protein excretion. Kidney sections were examined by HE and PAS staining, immunohistochemistry and transmission electric microscopy (TEM). The expression of Rho-kinase mRNA and P27 mRNA in kidney were detected by RT-PCR. It was found that the 24-h urine protein excretion in model group was increased significantly as compared with sham group (P<0.01). But this increase was significantly suppressed by fasudil (P<0.05). At 4 week, the foot process effacement in podocytes, mesangial proliferation and ECM accumulation were observed in model group, presenting as focal segmental glomerulosclerosis. But in the treatment group, the fasudil alleviated glomerular injury, with proliferating cell nuclear antigen (PCNA)-positive cell infiltration ameliorated and the expression of P27 increased. The expression of Rho-kinase mRNA was significantly enhanced in model group and was suppressed in treatment group. Moreover, fasudil up-regulated the mRNA expression of P27. Our study demonstrated that the glomerulosclerosis was substantially ameliorated by inhibiting the expression of Rho-kinase. It is suggested that Rho-kinase pathway is involved in the renal injury and the inhibition of Rho-kinase may constitute a therapeutic strategy for the treatment of renal injury.

AIM:To study the potential pathological role of abnormal expression of endogenous angiopoietins in progressive glomerulosclerosis.METHODS:80 male Wistar rats were randomly allocated into sham operation group(sham,n=25),unilateral nephrectomy group(UNx,n=25)and UNx+daunorubicin(DRB)group(n=30).The rats in DRB group were intravenously injected with DRB(5 mg/kg)on the seventh and the fourteenth day respectively after excising one kidney.Then,at week 1,2,4,6 and 8,5,male Wistar rats from each group were taken randomly for determining 24 h urinary protein quantitative measurement(24hUPQ),BUN,Scr,and the kidneys were examined by electronic microscope,PAS staining,immunohistochemical staining and in situ hybridization histochemistry.RESULTS:There was a trend towards an increase respectively in levels of 24hUPQ,Bun,Scr,GSI in DRB from week 2 to week 8.Electronic microscope revealed that podocyte injury presented in DRB group.Expression of Ang1 mRNA and protein in glomerulus in DRB group decreased,while expression of Ang2 protein in glomeruli in DRB group increased.In DRB group,expression of Ang1 protein had a negative correlation with 24hUPQ,BUN,Scr,GSI,expression of Ang2 protein and CoIV protein.Expression of Ang2 protein had a positive correlation with 24hUPQ,BUN,Scr,GSI,expression of CoIV protein.CONCLUSION:Podocyte injury may lead to glomeruli abnormally express angiopoietins.A decrease in expression of Ang1,and upregulation in expression of Ang2 may facilitate progressive glomerulosclerosis in the rat.

AIM: To establish a model of subtotal nephrectomy (SNx) and investigate the changes of apoptosis and apoptosis-related genes (Bax, bcl-2, caspase-3, caspase-8 and caspase-9) in the rat remnant kidney. METHODS: Remnant kidneys were produced in adult male SD rats by 5/6 nephrectomy. The renal function and histopathological changes were evaluated at 1, 2, 4, 8, 12, 16, 26 and 40 weeks after operation. The tissues of remnant kidneys were collected to detect apoptosis cells by in situ end-labeling of cleaved DNA (TUNEL) and proliferating cells by determining the proliferating cell nuclear antigen (PCNA). The expression of Bax, bcl-2, caspase-3, caspase-8 and caspase-9 was measured by RT-PCR and Western blotting. The proteins were detected by immunohistochemistry staining. The relation between apoptosis, proliferation, glomerulosclerosis and renal interstitial fibrosis was also observed. RESULTS: The results showed the renal pathological dynamic changes in 5/6 nephrectomy remnant kidneys were tubule-interstitial inflammation and fibrosis, as well as glomerulosclerosis. There were transient increases in both proliferating and apoptotic processes in glomerulus, tubules and interstitium. Apoptosis was increased and most of apoptotic cells were detected in tubular epithelial cells and interstitial area. The mRNA and protein expression of Bax, caspase-3, caspase-8 and caspase-9 were increased in all course, and peaked at week 4 and 40 in the SNX rats. The successive changes of these parameters were parallel to the level of focal inflammation in interstitium. Glomerulosclerosis index was related with focal inflammation cells and 24 hours urine protein (r=0.788, 0.822; P

AIM:To observe the expression of connective tissue growth factor(CTGF)in unilateral ureteral obstruction(UUO)rats,and to explore its pathogenic role in renal tubulointerstitial fibrosis.METHODS:48 Wistar rats were randomly divided into sham-operated and UUO group.The rats were sacrificed at day 1,3,7,and 14.The degree of tubulointerstitial damage was scored according to the Masson staining.The mRNA and protein levels of CTGF,transforming growth factor-?1(TGF-?1),collagen Ⅰ(Col Ⅰ),and plasminogen activator inhibitor-1(PAI-1)were detected by reverse transcriptional-polymerase chain reaction(RT-PCR)and immunohistochemistry,respectively.Expression of CTGF protein in the kidney was also assessed using Western blotting.RESULTS:TGF-?1 mRNA level began to increase as early as 1 day after UUO.This increase was followed by the elevation of CTGF mRNA level,which began to increase at third days after UUO(P

Objective:To observe the therapeutic effect and safety of warfarin on patients with atrial fibrillation. Methods:A total of 126 patients with atrial fibrillation from our hospital during Jun 2012-Jun 2013 were selected. According to hiding number random method,they were divided into aspirin group (n=63)and warfarin group (n=63).Coagulation function,blood lipid levels and end-point events were compared between two groups.Results:Compared with aspirin group,after treatment,there were significant reductions in levels of total cholesterol [(5.8 ±0.5)mmol/L vs.(5.2±0.7)mmol/L],triglyceride [(2.6±0.4)mmol/L vs.(2.4±0.3)mmol/L]and low density lipoprotein cholesterol [(2.7±0.5)mmol/L vs.(2.4±0.3)mmol/L],significant rise in level of high den-sity lipoprotein cholesterol [(1.1±0.2)mmol/L vs.(1.3±0.2)mmol/L],prothrombin time [(28.3±11.7)s vs. (36.9±10.4)s]and it′s international normalized ratio [(1.9±0.4)vs.(2.4±0.5)]in warfarin group,P <0.05 all.Incidence rate of endpoint events such as cerebral infarction and peripheral artery embolism etc.in warfarin group was significantly lower than that of aspirin group (3.17% vs.23.81%,P <0.01).The incidence rates of complications were 23.81% and 26.98% in warfarin group and aspirin group respectively,and they had no signifi-cant difference,P >0.05. Conclusion:For atrial fibrillation,the therapeutic effect and safety of warfarin is better than that of aspirin,is worth extending.

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

Actins ; metabolism ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; metabolism ; pathology ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Sarcoma ; metabolism ; pathology ; Vimentin ; metabolism

Objective To evaluate the value of cough test in the tension-free vaginal tape (TVT)procedure.Methods A cohort of 85 women with stress urinary incontinence underwent the TVT procedure with cough test (n =41) or without cough test (n =44).Patients in cough test group were performed according to the Ulmsten’s method strictly,with the stress of tape adjusted in light of cough test; whereas in other 44 operations,the tape was placed on the urethral tract without stress,and no cough test was performed.The urine catheter was removed after 48 hours postoperatively and follow-up evaluation was carried out at 12 month postoperatively.Results TVT procedure was carried out successfully in all patients by a single experienced surgeon.Four cases of urinary retention and 5 cases of voiding difficulty were observed in the cough test group.However,urinary retention or voiding difficulty was not detected in the nun-cough test group.Based on the twelve-month follow-up results,the cure rate was 92.6％ (38/41) in the cough test group and 93.1％ (41/44) in the non-cough test group.Flow-pressure study indicated that 11 cases in cough test group were in the obstruction zone,while only 3 cases in the obstruction zone were detected in the non-cough test group.Conclusions TVT is a safe as well as effective minimally invasive surgical procedure to treat female stress urinary incontinence.However,Adjusting stress of tape in accordance with cough test during the TVT may potentially increase the incidence of urinary dysfunction postoperatively.Therefore,no convincing evidence was gained to support the efficacy of cough test during TVT in terms of preventing postoperative voiding dysfunction.