Change in plasma H2S level and therapeutic effect of H2S supplementation in tubulointerstitial fibrosis among rats with unilateral ureteral obstruction / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the level in plasma hydrogen sulfide (H2S) and the expression of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) (two key synthetases for endogenous H2S generation in the kidney) in obstructed kidney tissue among rats with tubulointerstitial fibrosis (TIF) induced by unilateral ureteral obstruction (UUO), and to explore the role of H2S in TIF.</p><p><b>METHODS</b>Ninety-six male Sprague-Dawley rats were randomly divided into sham-operated, model, low-dose NaHS and high-dose NaHS groups (n=24 each). TIF was induced by UUO in the model, low-dose NaHS and high-dose NaHS groups. The low-dose and high-dose NaHS groups were intraperitoneally injected with NaHS (1.4 and 7.0 μmol/kg respectively) twice daily immediately after operation, and the sham-operated and model groups were intraperitoneally injected with an identical volume of normal saline. In each group, 8 rats were randomly selected and sacrificed at 7, 14 or 21 days after operation. Plasma H2S concentration was measured by deproteinization. The obstructed kidney tissue was subjected to hematoxylin and eosin staining and Masson staining, and the renal tubulointerstitial injury was evaluated under a microscope. mRNA and protein expression of CBS and CSE in the obstructed kidney tissue was measured by RT-PCR and immunohistochemistry respectively.</p><p><b>RESULTS</b>The degree of UUO-induced renal tubulointerstitial injury was negatively correlated with plasma H2S concentration in (r=-0.891, P<0.01). With H2S supplementation, renal tubulointerstitial injury was reduced (P<0.01), the expression of mRNA and protein of CBS and CSE in the kidney tissue and plasma H2S level were upregulated (P<0.01), and the degree of TIF was reduced (P<0.01). There were no significant differences in plasma H2S level and mRNA and protein expression of CBS and CSE between the low-dose and high-dose NaHS groups (P>0.05).</p><p><b>CONCLUSIONS</b>H2S is involved in the development of UUO-induced TIF, and the CBS/H2S and CSE/H2S systems play key roles in this process. H2S supplementation can delay the progression of TIF.</p>

Effect of hydrogen sulfide on expressions of ectodermal dysplasia-1 and kidney injury molecule-1 of renal interstitial in rats with unilateral ureteral occlusion / 中华实用儿科临床杂志

Objective To investigate the effects of hydrogen sulfide (H2S) on the tubular interstitial fibrosis and on the levels of kidney injury molecule-1 (KIM-1) and ectodermal dysplasia-1 (ED-1) in the process of renal interstitial fibrosis in rats with unilateral ureteral occlusion(UUO).Methods Ninety-six Sprague-Dauley (SD) male rats were divided into 4 groups randomly:sham-operated group (n =24),model group (n =24),low-dose therapy group (n =24) and high-dose therapy group(n =24).The rats in the model group and treatment groups were ligated at the left ureter and UUO was induced,meanwhile,the rats in the control group were free from the left ureter ligation.Rats received sodium hydrosulfide(NaHS) in traperitoneatly(1.4 μmol/kg,twice a day),and NaHS(7.0 μmol/kg,twice a day),respectively.Rats in sham-operated group and the model group were injected intraperitoneally with identical voluminal 9 g/L saline.Eight rats in each group were sacrificed randomly at the 7 days,14 days and 21 days,respectively.The concentration of plasma H2S was detected.Renal tubular interstitial damage and interstitial fibrosis were evaluated with routine HE staining and Masson staining under microscope,and both of them were used to evaluate the obstruction of renal histopathological changes.The expressions of ED-1 and KIM-1 were measured with immunohistochemical staining.Results 1.The pathological findings showed that the renal tubular interstitial changes were not obvious in the shamoperated group.The tubular epithelial cells in the model group and treatment groups showed swelling and vacuoles degeneration,with renal interstitial broadening,interstitial cells and extracellular matrix increasing.The renal tubular interstitial pathological injury of model group and treatment group were more serious than those in the sham-operated group at each time point(P ＜ 0.05).The renal tubular interstitial pathological injury of the treatment groups were obviously lower than that in the model group(P ＜0.05).However,there was no statistically significant difference between highdose therapy group and low-dose therapy group(P ＞ 0.05).2.Immunohistochemical analysis showed that expressions of ED-1 and KIM-1 in renal tubular interstitices in the model group and the treatment groups were higher than those in the sham-operated group at each time point(P ＜ 0.05).The expressions of ED-1 and KIM-1 in renal tubular interstitices in the treatment groups were obviously lower than those in the model group(P ＜ 0.05).There was no statistically significant difference between the high-dose therapy group and the low-dose therapy group(P ＞0.05).3.Plasma H2S levels in model group and treatment group were lower than those in the sham-operated group at each time point (P ＜ 0.05).The plasma H2S level of the treatment group was obviously higher than that in the model group(P ＜ 0.05).However,there was no statistically significant difference between high-dose therapy group and low-dose therapy group (P ＞0.05).Conclusions H2S implements renal protection effect partly by reducing the expression of ED-1 and KIM-1 in tubule interstitices to ease tubular interstitial fibrosis.

Effects of bicyclol on renal PAI-1 expression in rats with uniliteral ureteral obstruction / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the protective effects of bicyclol against renal interstitial fibrosis and possible mechanisms of the protection.</p><p><b>METHODS</b>Eighty-one Sprague-Dawley (SD) rats were randomly assigned to a sham-operated group and UUO groups with and without bicyclol treatment. A rat model of renal interstitial fibrosis was prepared by unilateral ureteral obstruction (UUO). Renal tissues were examined by hematoxylin & eosin and Masson staining on 7, 14 and 21 days. Immunhistochemistry was used for determining plasminogen activator inhibitor-1(PAI-1) expression in the renal interstitium. PAI-1 mRNA expression in renal tissues was semi-quantitatively determined by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The relative areas of renal interstitial fibrosis in the bicyclol-treated UUO group 7, 14 and 21 days after operation were (9.6 ± 0.6)%, (16.8 ± 0.8)% and (33.6 ± 1.6)% respectively, which were significantly lower than those in the untreated UUO group [13.0 ± 0.7)%, (25.8 ± 1.5)% and (53.2 ± 2.5)% respectively] (P<0.05). The levels of protein and mRNA expression of PAI-1 in the bicyclol-treated UUO group decreased significantly compared with those in the untreated UUO group 7, 14 and 21 days after operation (P<0.05).</p><p><b>CONCLUSIONS</b>Bicyclol can alleviate renal interstitial injury and renal interstitial fibrosis caused by UUO in rats, possibly through a downregulation of renal PAI-1 expression.</p>

Effects of Silymarin on Expressions of Nuclear Factor Kappa B and Intercellular Adhesion Molecule-1 in Renal Tissue of Rats with Tubulointerstitial Fibrosis / 实用儿科临床杂志

Objective To investigate the effects of silymarin on expressions of nuclear factor kappa B(NF-?B) and intercellular adhesion molecule-1(ICAM-1) in the kidneys of rats with unilateral ureteral obstruction(UUO)-induced renal fibrosis.Methods Seventy-two male Sprague-Dawley rats were randomly divided into 3 groups: sham-operated group(n=24),operated group(n=24) and silymarin treated group(n=24).Renal tubulointerstitial fibrosis model was established via UUO.Silymarin was given by gavage with 30 mg/(kg?d) in silymarin treated group,and the same volume normal saline was given by gavage in operated group and sham-operated group.In each group,8 rats were killed at 7,14 and 21 d after operation.Histological changes were observed in tubulointerstitial injury under microscope.The expressions of NF-?B and ICAM-1 in renal tissue were determined with immunohistochemical method.Results Tubuloin-terstitial injury scores in operated group at 7,14 and 21 d were 1.168?0.108,1.776?0.064 and 2.301?0.157,respectively,and Tubulointerstitial injury scores in the treated group at 7,14 and 21 d were 1.043?0.114,1.677?0.083 and 2.084?0.201,respectively.Tubulointerstitial injury scores in silymarin treated group were significantly lower than those in operated group(Pa

Intervention Effect of Silymarin Attenuate Tubulointerstitial Fibrosis in Rats with Unilateral Ureteral Obstruction / 实用儿科临床杂志

Objective To observe the influence of silymarin on expressions of transforming growth factor-?1(TGF-?1) and collagen type Ⅲ(Col Ⅲ) in rats with experimental tubulointerstitial fibrosis(TIF) induced by unilateral ureteral obstruction(UUO).Methods Se-venty-two Sprague-Dawley rats were randomly divided into 3 groups:sham operation group(n=24),model group(n=24) and silymarin treatment group(n=24).The rats in model group and treatment group were operated by ligation of left-ureter.The rats in sham opera-tion group operated by dissociating left-ureter were taken as controls.Rats in treatment group were fed with silymarin [30 mg/(kg?d)]24 h before operation,and rats in model group and sham operation group were treated by intragastric administration with the same volume nomal saline at the same time.Eight rats were killed at day 7,14,and 21,respectively.The score of TIF changes,histologically,was evaluated under light microscope.Expressions of TGF-?1 and Col Ⅲ in tubulointerstitial tissue in 3 groups were investigated by immunohistochemistry.Results 1.The TIF pathological index in treatment group was less than that in model group,but more than sham operation group at day 14 and 21(Pa

Efficacy of Mycophenolate Mofetil on Children with Steroid-Dependent Nephrotic Syndrome / 实用儿科临床杂志

Objective To evaluate the clinical efficacy and safety of mycophenolate mofetil(MMF)on children with steroid-dependent nephrotic syndrome(SDNS).Methods Sixteen children with SDNS,diagnosed at onset,included 12 males and 4 females,aged(5.0?1.6) years,were administrated with MMF[25 mg/(kg?d)] and low-dose prednisone[0.5-1.0 mg/(kg?d),average 0.67 mg/(kg?d)].MMF was reduced to half of initial dosage after 6 months and maintained for 3 months,while dosage of prednisone was tapered gradually based on patients disease profile.Twenty-four hours urinary protein excretion,serum creatinine and blood urea nitrogen,liver function were conducted regularly,respectively.The clinical efficacy and safety were assessed after 3 months treatment.Results Thirteen of 16 patients treated with MMF and prednisone remained in complete remission.Three children remained remission partly.Difference markedly was observed in 24 hours urinary protein excretion and serum albumin before and after treatment.Conclusions MMF is an effective and safe immunosuppressive agent for children with SDNS.

Effect of Lovastatin on Plasminogen Activator Inhibitor-1 and Collagen Type Ⅳ in Rats with Glomerularsclerosis / 实用儿科临床杂志

Objective To observe the effect of lovastatin on plasminogen activator inhibitor -1 (PAI-1) and collagen type Ⅳ in rats with glomerularsclerosis induced by adriamycin,and to discuss its mechanism of protective effects on kidneys.Methods Twenty-four male Wistar nephritic rats induced by adriamycin were randomly divided into 3 groups:control,hyperlipidemia and lovastatin treatment group.They were fed 12 weeks.Urinary protein excretion and serum lipid were assayed,then renal glomerularsclerosis index,the expression of PAI-1 and collagen type Ⅳ were observed.Results Serum total cholesterol,triglycerides,low-density lipoprotein,urinary protein excretion,renal glomerularsclerosis index were significantly lower in treatment group than those in hyperlipidemia group.Expression of PAI-1 and collagen type Ⅳ,and number of foamcells were also sharply lower in treatment group than those in hyperlipidemia group.Conclusions Lovastatin not only reduces proteinuria,improves renal function,but also modulates glomerularsclerosis by inhibiting activity of PAI-1 and decreasing accumulation of collagen type Ⅳ.The mechanism of renal protective effect is independent of a reduction of circulating cholesterol.

The expression of glomerulosclerosis by benazepril and its relationship with apoptosis of kidney cells / 实用儿科临床杂志

Objective To study the effects of angiotensin converting enzyme inhibitor benazepri1 on apoptosis and the expression of Fas and FasL in the kidney of rats with adriamycin-indued nephritic glomeruosclerosis.Methods After uninephrectomy and the injection of adriamycin induced rats model with glomerulosclerosis, benazapril(6 mg/kg) was delivered daily by gavage to the rats in therapeutic groups for 12 weeks.Apoptosis was examined by means of terminal-deoxynucleotidyl trans ferase mediated d-UTP nick end label ling(TUNEL) and immunohistochemistry was utlized to detect the expression of Fas and FasL.Software of pathological analysis quantitated the level of Fas and FasL.Results Compared with those of the control group, the kidney of model group had moresevere glomerulosclerosis, much more apoptotic cells and higher level of exprssion of Fas and FasL. The degree of glomeruloscleroais, the nuxner of apoptotic cells and the level of expression of Fas and FasL were ameliofated by benazepril treatment.Conclusion Benazepril may suppress the excessive apoptosis of kidney cell by lowering the expression of the protin correlatng apoptosis Fas and FasL,so as to postpone the process of glomeruosclerosis.