title: Anti-inflammatory effects of triptolide on IgA nephropathy in rats.
abstract: IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague-Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200 μg/kg/d intragastrically) from 12 to 28 weeks. At Week 28, the rats was sacrificed, kidneys and blood samples were collected for further analysis. Our data shown that IgAN rat model showed marked deterioration of proteinuria together with higher levels of the urine protein:creatinine ratio compared to the normal control. Animals that underwent intermittent exposure to triptolide treatment exhibited significant improvements in the functional parameters without severe side effects. Rats developing IgAN had profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, while triptolide treatment significantly attenuated it. We also observed that treatment with triptolide significantly decreases serum levels of IL-1β and IL-18, and may exerted anti-inflammatory effects by down-regulating NLRP3 and TLR4 expression. Our study clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Liyu
authors.initials: L
authors.lastname: He
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Peng
authors.affiliation: b Department of Nephrology , The First Affiliated Hospital of Changde Vocational Technical College , Changde , Hunan , People's Republic of China , and.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Liu
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Tang
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Fuyou
authors.initials: F
authors.lastname: Liu
authors.affiliation: c Department of Nephrology , The First People's Hospital of Xiangtan City , Xiangtan , Hunan , People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Zhou
authors.affiliation: a Department of Nephrology , The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan , Changsha , Hunan , People's Republic of China .
authors.forename: Youming
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002352:Carrier Proteins / Q000276:immunology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D004224:Diterpenes; D004852:Epoxy Compounds; C000594089:IL1B protein, rat; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D010616:Phenanthrenes; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C001899:triptolide
keywords: IgA nephropathy; NLRP3; TLR4; inflammation; triptolide