Research on protective mechanism of ibuprofen in myocardial ischemia-reperfusion injury in rats through the PI3K/Akt/mTOR signaling pathway
Authors: X-Q Ding
Y Chi
Q Ma
C Wang
X Qin
J Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ibuprofen; myocardial ischemia-reperfusion injury; PI3K/Akt/mTOR signaling pathway; rats; protective mechanism
Affiliations: First Community, People's Hospital of Rizhao Affiliated to Jining Medical University, Rizhao, China. .

Abstract:  Objective: To study the protective mechanism of ibuprofen (Ib) in myocardial ischemia-reperfusion (I/R) injury in rats, and to analyze its regulatory effect on the phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Materials and methods: The rat model of myocardial I/R injury was established via ligation of the left main coronary artery (LCA) for 30 min and then reperfusion for 120 min. A total of 36 Sprague-Dawley (SD) rats were randomly divided into sham group (S group, n=12), model group (I/R group, n=12) and Ib group (n=12). The levels of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in each group were detected. The rats were executed, the heart was isolated and the area of myocardial infarction was determined via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1) and apoptosis-related proteins in myocardial tissues in each group were detected via Western blotting. Moreover, the content of inflammatory factors in myocardial tissues in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The expression levels of related proteins in the PI3K/Akt/mTOR signaling pathway in myocardial tissues were further analyzed. Results: Compared with those in S group, the levels of CK-MB and LDH were significantly increased (p&lt;0.01), the area of myocardial infarction was significantly increased (p&lt;0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were increased (p&lt;0.01), while Bcl-2/Bax declined (p&lt;0.01), the content of interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) in myocardial tissues was increased (p&lt;0.01), while the content of IL-10 declined (p&lt;0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly decreased (p&lt;0.01) in I/R group. Compared with those in I/R group, the levels of CK-MB and LDH were significantly decreased (p&lt;0.01), the area of myocardial infarction was significantly decreased (p&lt;0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were decreased (p&lt;0.01), while Bcl-2/Bax was increased (p&lt;0.01), the content of IL-1, IL-6 and TNF-α in myocardial tissues declined (p&lt;0.01), while the content of IL-10 was significantly increased (p&lt;0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly increased (p&lt;0.01) in Ib group. Conclusions: Ib can activate the PI3K/Akt/mTOR signaling pathway, reduce the release of inflammatory factors and apoptosis, and alleviate the myocardial I/R injury in myocardial cells in rats. 

Retracted: No

PubPeer comments:
 Figure 3A.  Protein expression levels in myocardial tissues in each group. A, Protein band . Below, Figure 5A from [Li Wang (2019)] :  Expression levels of apoptosis-related proteins detected via Western blotting. A, Protein band ![file] Same loading control. ,