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.
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 diabeticrats 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: Alexander Grotemeyer; Rhonda Leah McFleder; Jingjing Wu; Jörg Wischhusen; Chi Wang Ip Journal: Front Immunol Date: 2022-05-18 Impact factor: 8.786
Authors: Enrico Ragni; Laura Mangiavini; Marco Viganò; Anna Teresa Brini; Giuseppe Michele Peretti; Giuseppe Banfi; Laura de Girolamo Journal: Clin Pharmacol Ther Date: 2020-06-22 Impact factor: 6.903
Authors: Vincent K C Yan; Xiaodong Li; Xuxiao Ye; Min Ou; Ruibang Luo; Qingpeng Zhang; Bo Tang; Benjamin J Cowling; Ivan Hung; Chung Wah Siu; Ian C K Wong; Reynold C K Cheng; Esther W Chan Journal: Adv Ther (Weinh) Date: 2021-05-20