title: Enalapril inhibits tubulointerstitial inflammation and NLRP3 inflammasome expression in BSA-overload nephropathy of rats.
abstract: OBJECTIVE
  Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats.
  
  
  METHODS
  Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg(-1)·d(-1), ip), or BSA plus enalapril (0.5 g·kg(-1)·d(-1), po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot.
  
  
  RESULTS
  BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68(+) cells (macrophages) and CD3(+) cells (T lymphocytes), particularly of CD20(+) cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril.
  
  
  CONCLUSIONS
  Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Ding
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Ri-ning
authors.initials: RN
authors.lastname: Tang
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Lin-li
authors.initials: LL
authors.lastname: Lv
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Kun-ling
authors.initials: KL
authors.lastname: Ma
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins; D020170:Caspase 1 / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009392:Nephrectomy / Q000379:methods; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D012710:Serum Albumin, Bovine; D004656:Enalapril; D020170:Caspase 1