Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury in rats via RhoA/ROCK1 signaling pathway
Authors: G-X Fei
Z-Y Zhang
C-L Ge
Y Xie
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Oxycodone; Myocardial ischemia-reperfusion injury; RhoA/ROCK1 signaling pathway; Sprague-Dawley rats; Bcl-2
Affiliations: Department of Anesthesiology, Xuhui District Central Hospital, Shanghai, China. .

Abstract:  Objective: The purpose of this study was to investigate the effect of oxycodone on myocardial ischemia-reperfusion injury in rats through the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway. Materials and methods: A total of 48 Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group, oxycodone group, and inhibitor group, with 12 rats in each group. The rats in the sham operation group only underwent thoracotomy without ischemia-reperfusion injury, those in the model group were used to prepare the myocardial ischemia-reperfusion model with normal saline intervention, those in the oxycodone group were used to prepare the myocardial ischemia-reperfusion model with oxycodone intervention, and those in the inhibitor group were utilized to prepare the myocardial ischemia-reperfusion model with AG490 intervention. Then, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) were detected by immunohistochemistry, the relative protein expressions of RhoA and ROCK1 were examined via Western blotting, and the messenger ribonucleic acid (mRNA) expressions of Bcl-2 and BAX were measured by quantitative Polymerase Chain Reaction (qPCR). Thereafter, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was adopted for apoptosis detection, and the levels of creatine kinase-muscle/brain (CK-MB), and cardiac Troponin I (cTnI) in serum were detected using an automatic biochemical analyzer. Results: Immunohistochemistry results showed that compared with those in the sham operation group, the positive expression of BAX was remarkably increased (p&lt;0.05), while that of Bcl-2 was significantly decreased (p&lt;0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group and inhibitor group had an evidently reduced positive expression of BAX (p&lt;0.05) and an evidently raised positive expression of Bcl-2 (p&lt;0.05). No differences were found in the positive expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p&gt;0.05). According to Western blotting results, the relative protein expressions of RhoA and ROCK1 in the model group, oxycodone group, and inhibitor group were notably increased compared with those in the sham operation group (p&lt;0.05). In comparison with those in the model group, the relative protein expressions of RhoA and ROCK1 in the oxycodone group and inhibitor group were predominantly reduced (p&lt;0.05). There were no differences in the relative protein expressions of RhoA and ROCK1 between oxycodone group and inhibitor group (p&gt;0.05). Moreover, it was discovered from qRT-PCR results that compared with those in the sham operation group, the mRNA expression of BAX was markedly raised (p&lt;0.05), whereas that of Bcl-2 was decreased predominantly (p&lt;0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group, and inhibitor group had an evidently reduced mRNA expression of BAX (p&lt;0.05) and a significantly raised mRNA expression of Bcl-2 (p&lt;0.05). No differences were found in the mRNA expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p&gt;0.05). In addition, TUNEL assay results manifested that compared with sham operation group, model group, oxycodone group, and inhibitor group had a markedly elevated apoptosis rate (p&lt;0.05). In comparison with the model group, the apoptosis rate in oxycodone group and inhibitor group was remarkably reduced (p&lt;0.05). There was no difference in the apoptosis rate between oxycodone group and inhibitor group (p&gt;0.05). According to biochemical analysis results, the serum levels of CK-MB and cTnI in model group, oxycodone group, and inhibitor group were significantly increased compared with those in the sham operation group, with statistically significant differences (p&lt;0.05). The levels of serum CK-MB and cTnI in the oxycodone group and inhibitor group were substantially lowered in comparison with those in the model group, displaying statistically significant differences (p&lt;0.05). Besides, the levels of serum CK-MB and cTnI in the oxycodone group were not different from those in the inhibitor group (p&gt;0.05). Conclusions: Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury by suppressing the RhoA/ROCK1 signaling pathway. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. , 
 Withdrawn. https: www.europeanreview.org article 23550 *Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cLong noncoding RNA CASC2 alleviates the growth, migration and invasion of oral squamous cell carcinoma via downregulating CDK1, by H.-B. Xing, H.-M. Qiu, Y. Li, P.-F. Dong, X.-M. Zhu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4777-4783u2013DOI: 10.26355 eurrev_201906 _18060u2013PMID: 31210307u201d has been withdrawn.* *The Publisher apologizes for any inconvenience this may cause.* ,