title: Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes.
  
  
  METHODS
  The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β1 (TGF-β1) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay.
  
  
  RESULTS
  Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β1 and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups.
  
  
  CONCLUSIONS
  Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β1 and mTOR.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Qiao
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Changdong
authors.initials: C
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D015536:Down-Regulation / Q000502:physiology; D005355:Fibrosis / Q000517:prevention & control; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D016212:Transforming Growth Factor beta; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D007052:Ibuprofen