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<p><b>OBJECTIVE</b>To investigate RANK-RANKL expression in the kidneys of a rat model of puromycin aminonucleoside nephropathy (PAN).</p><p><b>METHODS</b>Thirty-six SD rats were randomly divided into PAN model group and normal control group. PAN was induced by a single intravenous injection of 100 mg/kg puromycin aminonucleoside. Serum creatinine and 24-hour urinary protein were measured on days 3, 7, and 14 after the injection, and renal pathologies were assessed with optical and immune transmission electron microscopy. The expression of RANK and RANKL in the kidneys was examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.</p><p><b>RESULTS</b>The PAN model rats showed massive proteinuria and elevated serum creatinine on day 3, which peaked on day 7. RANK-RANKL protein and mRNA expressions in PAN model group was higher than those in the control group. In the PAN rats, RANK was expressed mainly on the top cell membrane and in the cytoplasm of renal podocytes with a significantly increased expression level compared with that in the control group.</p><p><b>CONCLUSION</b>The PAN rat model shows aberrant RANK and RANKL expressions in the podocytes, indicating their contribution to podocyte injury in PAN.</p>
Subject(s)
Animals , Female , Male , Rats , Creatinine , Blood , Kidney , Metabolism , Kidney Diseases , Metabolism , Pathology , Podocytes , Metabolism , Proteinuria , Pathology , Puromycin Aminonucleoside , RANK Ligand , Metabolism , Rats, Sprague-Dawley , Receptor Activator of Nuclear Factor-kappa B , MetabolismABSTRACT
Objective To measure the renal cortex blood flow leVel in Patients with stage 3-4 chronic kidney disease, and to obserVe the effect of Probucol on renal cortex blood flow and renal function. Methods Twenty Patients with stage 3-4 chronic kidney disease in our hosPital were randomly diVided into treatment grouP ( 10 Patients ) and obserVation grouP ( 10 Patients). Ten healthy subjects were chosen as the control grouP. Dynamic sonograPhic tissue Perfusion measurement (DTPM) was used to eValuate the mean flow intensity (Imix),mean flow Velocity (Vmix) and tissue resistance index (TRI) in the three grouPs. Patients in the obserVation grouP were treated with standard theraPy;the treatment grouP was giVen Probucol 500 mg,twice daily in addition to standard theraPy for 6 months. The renal cortex blood flow leVel after treatment was measured in the treatment grouP and obserVation grouP. The serum BUN,SCr,TC,TG,LDL,HDL,hs_CRP,ox_LDL,PA,ALB before and after treatment were measured and comPared between the treatment grouP and obserVation grouP. Results Imix and Vmix were significantly lower,and TRI was significantly higher in the treatment grouP and obserVation grouP than in the control grouP (P<0. 01). After 6 months of treatment,Imix and Vmix in the treatment grouP were significantly increased and TRI significantly decreased as comPared with the baseline and the control grouP (P<0. 01). After treatment,Imix and Vmix were significantly decreased and TRI was significantly increased in the obserVation grouP (P<0. 05). In the treatment grouP,the serum BUN,SCr,TC,TG,LDL,hs_CRP and ox_LDL decreased and PA,ALB and HDL increased after treatment as comPared with the baseline and the obserVation grouP (P<0. 05 or P<0. 01). Conclusion The renal cortex blood flow leVel is significantly lower in Patients with stage 3-4 chronic kidney disease than in the healthy PeoPle. Probucol can imProVe the renal cortex blood flow leVel significantly,Protect the renal function, and imProVe microinflammatory state,nutrition status and dysliPidemia.
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ObjectiveTo evaluate the effects of 1,25(OH)zD3 on podocyte apoptosis in kidney of puremyein aminonueleoside nephropathy (PAN) rats. Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups: PAN model group(PAN), 1,25 (OH)2D3 treated group (T, 0.2 μg·kg-1d-1 by garages) and normal control group (NC). PAN rat model was constructed by a single intravenous injection of 100 mg/kg body weight. Renal function and 24hour urinary protein were measured at day 3, 7, 14, 21 after PAN injection. The renal tissue morphology was observed by light and electron microscope. Podocyte apeptosis was evaluated by TUNEL. Protein expressions of nephrin, TGF-β1 and p-Smad2/3 were examined by immunofluoreacence, immunohistochemistry and Western blot, respectively. Results(1)The levels of serum creafinine, BUN and 24-h urinary protein [(20.26±4.87) mg vs (1.01±0.41) mg at day 7, P ＜0.01] were significantly higher and the number of glomerular pedocyte was significantly lower [(10.9±4.2)/glomerular volume vs (31.9±6.2)/glomerular volume at day 14, P＜0.01] in PAN group compared with NC group. T group rats had less urinary protein excretion [(9.95±3.82) mg/24 h, P＜0.01] and more glomerular podocytes compared with PAN group. (2) Distribution of nephrin expression was changed from linear to granular pattern in PAN rats on day 7, nephrin mRNA and protein expressions were markedly decreased(P＜0.01), while the number of apoptotic podocyte was increased in PAN group(P＜0.01). However, higher nephrin expression and less apoptotic podocytes were found in T group (P＜0.01). (3) Compared with NC group, the mRNA and protein expression of TGF-β1 and p-Smad2/3 were higher in PAN group (P＜0.01), while 1,25 (OH)2D3 treatment abrogated PAN-induced changes in the expression of TGF-β1 and p-Smad2/3 (P＜0.01). Conclusions 1,25 (OH)2D3 can significantly suppress PAN-induced podocyte apoptosis and ameliorate proteinnuria. The beneficial effect of 1,25(OH)2D3 on podocyte may contribute to direct suppression of TGF-β signaling.
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Objective To investigate the expression transforming growth factor?1(TGF-?1),Smad7 and connective tissue growth factor(CTGF) in rats with renal tubulointerstitial fibrosis and the effects of Gypenosides(GPs) treatment on expression of TGF-?,Smad7 and CTGF.Methods Unilateral ureteral Obstruction(UUO) rat animal models were used and the rats were divided into GPs group(Gypenosides 200 mg?Kg~(-1)?d~(-1) by gastric gavage from 3d before the obstruction to 14 days after the induction),model group and sham operated group.The expression of TGF-?1,Smad7 and CTGF in the obstructed kidneys was assessed by RT-PCR,immunohistochemistry and HE staining methods after 3,7,and 14d respectively.The degree of tubulointerstitial damage was scored by Masson staining methods.Results Compared with the sham operated group,the expressions of TGF-?1,CTGF mRNA and protein were markedly increased in UUO group,and the expression of Smad7 mRNA and protein was markedly decreased(all P
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Objective To investigate the regulation of cyclooxygenase-2 expression and mechanism of selective cyclooxygenase-2 inhibitor Celecoxib suppressing tubulointerstitial fibrosis of rats with unilateral ureteral obstruction(UUO) model. Methods The UUO models were induced by ligating the left ureter. Rats were randomly divided into bulofen group (group B), Celecoxib group (group R), model group (group C) and sham operation group (group S). Rats in group B were given bulofen 300mg?Kg~ -1?d~ -1, and in group R were given Celecoxib 10mg?Kg~ -1?d~ -1 by gastric gavage from 24 h before the obstruction to 14 days after the induction. Rats were sacrificed at 3d, 6d and 14d in batch after the UUO models were induced. The mRNA expressions of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), transforming growth factor-beta 1 (TGF-?1), and connective tissue growth factor (CTGF) were detected by RT-PCR. The protein expressions of TGF-?1, CTGF and ?-SMA were detected using immunohistochemistry and the content of cAMP was determined by radioimmuno-assay. Results Compared with group S, the mRNA expressions of COX-2, TGF-?1 and CTGF in group C increased markedly after UUO treatment, and the content of cAMP decreased. It showed no significant difference in the mRNA expressions of TGF-?1, CTGF and the content of cAMP for the Bulofen treatment in the UUO model. With the Celecoxib treatment, there was no significant difference on the mRNA expression of TGF-?1, but the content of cAMP increased and the expression of CTGF decreased. Conclusion The COX-2 plays an important role in lesion of tubulointerstitial. Selective cyclooxygenase-2 inhibitor can partially up-regulate the content of cAMP and down-regulate the expression of CTGF, the downstream factor of TGF-?1, which may postpone the renal interstitial fibrosis.
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Objective To investigate expression of connective tissue growth factor(CTGF) in the kidney of patients with type 2 diabetic mellitus(DM) as well as its clinical significance.Methods Fourty cases with DM were divided into three groups: normal albuminuric group(200 ?g/min,n=12).The urinary excretion rates of CTGF were determined by ELISA in all the cases and 30 subjects of control.Twenty cases of them received renal biopsy.Expression of CTGF in kidney among different groups were detected by immunohistochemical stainning.Results Expression of CTGF in kidney elevated significantly in DM as compared with group of normal control.At the same time the excretion rates of CTGF in DM groups were markedly higher than that in control(P