1.A Case of Gouty kidney.
Hyeung Ki CHOI ; Dai Bong OH ; Chong Soon WANG
Korean Journal of Urology 1971;12(4):413-417
Primary gout is an as yet undefined inborn error of metabolism characterized by hyperuricemia, recurrent attacks of acute arthritis ordinarily responsive to colchicine, and in many instances eventually by tophaus deposit of urate. Also secondary gouty symptom complexes can be induced by various causes. The kidney is involved about 15 ~ 20% of gout and represented clinically as albuminuria, which may persist for several decades before nitrogen retention ensues, and progressively reveal the impairment of concentrating ability and delayed excretion of PSP. This patient has been chronically suffered from the right flank pain and intermittent oliguria due to bilateral ureteral obstruction by uric acid stone and crystals for five years and exploratory operation for stone turned out as gouty kidney complicated in the polycystic kidney. The authors report this case with review of the literature.
Albuminuria
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Arthritis
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Colchicine
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Flank Pain
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Gout
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Humans
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Hyperuricemia
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Kidney*
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Metabolism
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Nitrogen
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Oliguria
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Polycystic Kidney Diseases
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Ureteral Obstruction
;
Uric Acid
2.Effect of losartan on renal expression of monocyte chemoattractant protein-1 and transforming growth factor-β(1) in rats after unilateral ureteral obstruction.
Yu-Yu HUANG ; An-Ping XU ; Shan-Shan ZHOU ; Jun-Zhou FU ; Hong DU
Journal of Southern Medical University 2011;31(8):1405-1410
OBJECTIVETo investigate the effect of losartan on the expression of monocyte chemoattractant protein-1 (MCP1) and transforming growth factor-β(1) (TGF-β(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and evaluate protective effect of losartan against reanal interstitial fibrosis.
METHODSRat models of UUO were treated with losartan at the routine dose, high dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days, the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN, K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were measured in the rats. MCP1 protein in the renal tissues was detected using immunohistochemistry, and MCP1 and TGF-β(1) mRNA expressions were assayed using RT-PCR.
RESULTSAs the UUO prolonged, Upro, TCP, tubular damage, %INT, and MCP1 and TGF-β(1) mRNA expressions all increased significantly (P<0.05). High and very high doses of losartan, compared with the routine dose, obviously reversed these changes.
CONCLUSIONHigh-dose losartan can effectively control blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF-β(1) expression in rats with UUO, and at a very high dose, losartan can more effectively reduce 24-h Upro than the high-dose group. High and very high doses of losartan offer better protective effect on the kidney in rats with UUO.
Animals ; Chemokine CCL2 ; metabolism ; Fibrosis ; etiology ; prevention & control ; Kidney ; metabolism ; pathology ; Losartan ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Ureteral Obstruction ; complications ; drug therapy
3.Active maintenance of endothelial cells prevents kidney fibrosis.
Seung Hee YANG ; Yong Chul KIM ; Jung Nam AN ; Jin Hyuk KIM ; Juhoh LEE ; Hee Yoon LEE ; Joo Youn CHO ; Jin Ho PAIK ; Yun Kyu OH ; Chun Soo LIM ; Yon Su KIM ; Jung Pyo LEE
Kidney Research and Clinical Practice 2017;36(4):329-341
BACKGROUND: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. METHODS: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. RESULTS: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks. Treatment with AUDA significantly ameliorated tubulointerstitial fibrosis by reducing fibroblast mobilization and enhancing endothelial cell activity. In an in vitro model of endothelial-to-mesenchymal transition (EndMT) using human vascular endothelial cells (HUVECs), AUDA prevented the morphologic changes associated with EndMT and reduced expression of fibroblast-specific protein 1. Furthermore, HUVECs activated by AUDA prevented the epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in a co-culture system. CONCLUSION: Our findings suggest that regulation of sEH is a potential target for therapies aimed at delaying the progression of kidney fibrosis by inhibiting EndMT and EMT.
Animals
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Coculture Techniques
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Endothelial Cells*
;
Epithelial Cells
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Epithelial-Mesenchymal Transition
;
Fibroblasts
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Fibrosis*
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Humans
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In Vitro Techniques
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Kidney*
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Metabolism
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Mice
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Renal Insufficiency, Chronic
;
Ureteral Obstruction
4.Active maintenance of endothelial cells prevents kidney fibrosis.
Seung Hee YANG ; Yong Chul KIM ; Jung Nam AN ; Jin Hyuk KIM ; Juhoh LEE ; Hee Yoon LEE ; Joo Youn CHO ; Jin Ho PAIK ; Yun Kyu OH ; Chun Soo LIM ; Yon Su KIM ; Jung Pyo LEE
Kidney Research and Clinical Practice 2017;36(4):329-341
BACKGROUND: Soluble epoxide hydrolase (sEH) expressed by endothelial cells catalyzes the metabolism of epoxyeicosatrienoic acids (EETs), which are vasoactive agents. METHODS: We used a unilateral ureteral obstruction mouse model of kidney fibrosis to determine whether inhibition of sEH activity reduces fibrosis, the final common pathway for chronic kidney disease. RESULTS: sEH activity was inhibited by continuous release of the inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA) for 1 or 2 weeks. Treatment with AUDA significantly ameliorated tubulointerstitial fibrosis by reducing fibroblast mobilization and enhancing endothelial cell activity. In an in vitro model of endothelial-to-mesenchymal transition (EndMT) using human vascular endothelial cells (HUVECs), AUDA prevented the morphologic changes associated with EndMT and reduced expression of fibroblast-specific protein 1. Furthermore, HUVECs activated by AUDA prevented the epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells in a co-culture system. CONCLUSION: Our findings suggest that regulation of sEH is a potential target for therapies aimed at delaying the progression of kidney fibrosis by inhibiting EndMT and EMT.
Animals
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Coculture Techniques
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Endothelial Cells*
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Epithelial Cells
;
Epithelial-Mesenchymal Transition
;
Fibroblasts
;
Fibrosis*
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Humans
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In Vitro Techniques
;
Kidney*
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Metabolism
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Mice
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Renal Insufficiency, Chronic
;
Ureteral Obstruction
5.Qianjin Wenwu decoction suppresses renal interstitial fibrosis by enhancing the degradation of extracellular matrix in mice with unilateral ureteral obstruction.
Chengshan JIN ; Xiaotian WU ; Yue YOU ; Yuing WANG ; Jing WU ; Along ZUO ; Yan ZHENG ; Jianpeng GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(4):253-262
Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats
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Mice
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Animals
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Ureteral Obstruction/metabolism*
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Kidney/metabolism*
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Tissue Inhibitor of Metalloproteinase-1/metabolism*
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Molecular Docking Simulation
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Rats, Sprague-Dawley
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Kidney Diseases/drug therapy*
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Extracellular Matrix/metabolism*
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Flavonoids/metabolism*
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Fibrosis
6.Role of integrin-linked kinase in renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on its expression in mice with obstructive nephropathy.
Feng HE ; Lu YU ; Jun-rong TONG ; Zheng-mao LUO ; Qi-zhi ZHU ; Yin WANG ; Jian-lin ZHANG
Journal of Southern Medical University 2009;29(5):909-913
OBJECTIVETo investigate the role of integrin-linked kinase (ILK) on renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on LIK expression in mice with obstructive nephropathy.
METHODSNormal male mice were randomly divided into sham-operated group (n=20), unilateral ureteral obstruction (UUO) group (n=28), and UUO with urokinase treatment group (uPA, n=28), and UUO was induced surgically in the latter two groups. The mice were sacrificed on days l, 3, 7 and 14 after the surgery, and renal interstitial fibrosis (RIF) was graded according to the result of Masson staining. The expression of ILK in the renal tissues of the rats was examined by immunofluorescence staining and Western blotting, and the expression of E-cadherin was detected by immunohistochemistry. RT-PCR was used to examine the mRNA expressions of ILK, E-cadherin and alpha-smooth muscle actin (alpha-SMA).
RESULTSThe expressions of ILK mRNA and protein were significantly increased in UUO group, but significantly decreased by treatment with uPA (P<0.05). The expression of alpha-SMA mRNA level was significantly increased, while E-cadherin decreased in mice with UUO on day 3 after the surgery. Treatment with uPA significantly inhibited such effects (P<0.05).
CONCLUSIONILK plays an important role in renal interstitial fibrosis by mediating epithelial-mesenchymal transition. Urokinase attenuates renal tubulointerstitial fibrosis in mice with UUO possibly by inhibiting ILK expression and preventing tubular epithelial-mesenchymal transition.
Animals ; Cell Transdifferentiation ; drug effects ; Epithelial Cells ; metabolism ; pathology ; Fibrosis ; Kidney Tubules ; metabolism ; pathology ; Male ; Mesoderm ; pathology ; Mice ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; physiology ; Ureteral Obstruction ; genetics ; metabolism ; pathology ; Urokinase-Type Plasminogen Activator ; pharmacology
7.Mechanism of transforming growth factor- β1 induce renal fibrosis based on transcriptome sequencing analysis.
Huanan LI ; Peifen LI ; Shanyi LI ; Xueying ZHANG ; Xinru DONG ; Ming YANG ; Weigan SHEN
Journal of Zhejiang University. Medical sciences 2023;52(5):594-604
OBJECTIVES:
To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis.
METHODS:
Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954).
RESULTS:
After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group.
CONCLUSIONS
TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.
Mice
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Animals
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Humans
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Transforming Growth Factor beta1/metabolism*
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Diabetic Nephropathies/pathology*
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Transcriptome
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Signal Transduction
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Kidney
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Ureteral Obstruction/pathology*
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Fibrosis
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Interferon Regulatory Factors
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Transforming Growth Factor beta/metabolism*
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DNA-Binding Proteins/metabolism*
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Transcription Factors/metabolism*
8.Effect of Astragalus mongholicus on expression of transforming growth factor- beta1 in SD rats with unilateral ureteral occlusion.
Chuan ZUO ; Xisheng XIE ; Yao DENG ; Junming FAN
China Journal of Chinese Materia Medica 2009;34(2):193-198
OBJECTIVETo study the effect of Astragalus mongholicus (AM) on the expression of transforming growth factor-beta1 (TGF-beta1) in SD rats with unilateral ureteral occlusion (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM.
METHODFifty-four Sprague-Dawley rats were randomly divided into 4 groups: sham-operation group, the UUO group and AM treatment group. After administration of AM (10 g kg(-1) d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of TGF-beta1 and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry staining sections. The mRNA of TGF-beta1 and alpha-SMA were reverse transcribed and quantified by real-time PCR. The expression of TGF-beta1 protein were assessed by Western blot.
RESULTRenal damage was exacerbated and the expression of alpha-SMA and TGF-beta1 were all significantly increased in UUO group compared with those of sham-operation group (P<0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of TGF-beta1 and alpha-SMA were significantly suppressed by AM treatment (P<0.05).
CONCLUSIONAM can ameliorate renal interstitial fibrosis induced by UUO in vivo. The mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression and suppression of tubular epithelial myofibroblast transdifferentiation in the progress of renal interstitial fibrosis.
Actins ; genetics ; Animals ; Astragalus Plant ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Kidney Tubules ; drug effects ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Transforming Growth Factor beta1 ; genetics ; Ureteral Obstruction ; metabolism ; pathology ; prevention & control
9.Effects of curcumin on the epithelial mesenchymal transition and TGF-beta/Smads signaling pathway in unilateral ureteral obstruction rats.
Yu LI ; Zhao-qing CHEN ; Ya-dong LI
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(9):1224-1228
OBJECTIVETo observe the effects of curcumin on the epithelial mesenchymal transition (EMT) and TGF-beta/Smads signal pathway in unilateral ureteral obstruction (UUO) rats.
METHODSUUO rat model was established. Rats were divided into the sham-operation group, the model group, the 1st curcumin group, and the 2nd curcumin group, respectively. From the 2nd day after surgery, rats of the 1st curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. From the 10th day after surgery, rats of the 2nd curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. Equal volume of normal saline was given to rats by gastrogavage in the sham-operation group and the model group. On the 28th day after surgery rats were killed. The renal tissues of the obstructed side were taken out. The distribution of mice alpha-smooth muscle actin (alpha-SMA) and E-cadherin expressions were observed using immunohistochemical method. Transforming growth factor-beta 1 (TGF-beta 1), P-Smad2, P-Smad3, and Smad7 expressions were detected by Western blot. TGF-beta 1, transforming growth factor-beta receptor I (TbetaRI), collagen-I (Col-I), and collagen-III (Col-III) mRNA expressions were detected by Real-time fluorescent quantitative PCR.
RESULTSalpha-SMA expressions were obviously enhanced, E-cadherin expressions obviously weakened, the protein expression levels of P-Smad2 and P-Smad3, protein and mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I mRNA, and Col-III mRNA obviously up-regulated, Smad7 protein expressions obviously decreased (all P<0.01) in the renal tissues of rats in the UUO group. In the 1st curcumin group and the 2nd curcumin group, the protein expressions of alpha-SMA, P-Smad2, P-Smad3, and TGF-beta 1; mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I, and Col-III obviously decreased (P<0.05, P< 0.01), while the protein expressions of E-cadherin and Smad7 obviously increased (P<0.05, P<0.01).
CONCLUSIONSCurcumin could intervene several sites of the TGF-beta/Smads signal transduction pathway of UUO rats, inhibit the occurrence of EMT of renal tubular epithelial cells, thus attenuating the tubulo-interstitial fibrosis.
Animals ; Curcumin ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Kidney Tubules ; cytology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; metabolism ; Transforming Growth Factor beta ; metabolism ; Ureteral Obstruction ; metabolism
10.Effects of bicyclol on renal PAI-1 expression in rats with uniliteral ureteral obstruction.
Chinese Journal of Contemporary Pediatrics 2011;13(6):509-513
OBJECTIVETo explore the protective effects of bicyclol against renal interstitial fibrosis and possible mechanisms of the protection.
METHODSEighty-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).
RESULTSThe 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).
CONCLUSIONSBicyclol can alleviate renal interstitial injury and renal interstitial fibrosis caused by UUO in rats, possibly through a downregulation of renal PAI-1 expression.
Animals ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Fibrosis ; Kidney ; chemistry ; drug effects ; metabolism ; pathology ; Male ; Plasminogen Activator Inhibitor 1 ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; drug therapy ; metabolism ; pathology