title: Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy.
abstract: OBJECTIVE
  The objective was to investigate the protective effects of rhein on renal histology change and the effects of rhein on renal tissue toll-like receptor (TLR) 4, TLR9, transforming growth factor-β1 (TGF-β1) expression in immunoglobulin A nephropathy (IgAN) rats.
  
  
  METHODS
  Bovine serum albumin-lipopolysaccharide-carbon tetrachloride 4 method was used to establish IgAN model. Thirty-two male sprague dawley rats were randomly divided into the control group, IgAN model group, rhein-prevented group, and rhein-treated group. 24-h urinary protein (UP), creatinine, urea, alanine aminotransferase (ALT), total protein (TP) contents in the serum of rats were detected with automatic biochemical analyzer and renal pathological changes were observed by the hematoxylin and eosin and periodic acid-Schiff staining. The glomerular deposition of IgA was measured by immunofluorescence staining. Real-time polymerase chain reaction and immunohistochemistry were used to detect renal tissue contents of TLR4, TLR9, TGF-β1 messenger ribonucleic acid and protein expression.
  
  
  RESULTS
  The biochemical parameters results of IgAN model rats showed that the 24-h UP excretion and ALT concentration were much higher, and TP concentration was much lower than those of the control group (P < 0.05). Granule-like or mass-like IgA depositions in the mesangial area, glomerular hypercellularity, hyperplasia of mesangial matrix, and tubulointerstitial fibrosis were found in IgAN group. Rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions.
  
  
  CONCLUSIONS
  Rhein significantly improved the serum and urine biochemical parameters, and attenuated the glomerular pathological changes and tubulointerstitial fibrosis in IgAN rats. The mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Medicine, Science and Technology College of Jiangxi Traditional Chinese Medicine University, Nanchang, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Histology and Embryology, Medical College of Nanchang University, Nanchang, China.
authors.forename: Huihong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Library, Medical College of Nanchang University, Nanchang, China.
authors.forename: Aixiang
authors.initials: A
authors.lastname: Fu
authors.affiliation: Department of Histology and Embryology, Medical College of Nanchang University, Nanchang, China.
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D064804:Urological Agents / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; C495347:Tlr4 protein, rat; C489640:Tlr9 protein, rat; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D053773:Transforming Growth Factor beta1; D064804:Urological Agents; C020491:rhein
keywords: Immunoglobulin A nephropathy; rhein; toll-like receptor; transforming growth factor-β1
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