Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats

Cardiology. 2015;131(2):97-106. doi: 10.1159/000375362. Epub 2015 Apr 15.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Cardiotonic Agents / pharmacology*
  • Diabetes Mellitus, Experimental / prevention & control
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Diabetic Angiopathies / prevention & control*
  • Down-Regulation / physiology
  • Fibrosis / prevention & control
  • Ibuprofen / pharmacology*
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Peptidyl-Dipeptidase A / metabolism
  • Rats, Sprague-Dawley
  • TOR Serine-Threonine Kinases / metabolism
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / physiology


  • Cardiotonic Agents
  • Transforming Growth Factor beta
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • Ibuprofen