Effect of propofol on myocardial ischemia/reperfusion injury in rats through JAK/STAT signaling pathway
Authors: D-B Li
Y Wang
X-P Zhang
Z-Y Xiao
D-N Hou
X Chen
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: propofol; myocardial ischemia/reperfusion injury; JAK/STAT signaling pathway; Sprague-Dawley rats; Bcl-2
Affiliations: Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. .

Abstract:  Objective: The aim of this study was to investigate the influences of propofol on myocardial ischemia/reperfusion injury in rats through the Janus kinase/signal transducers and the activators of transcription (JAK/STAT) signaling pathway. Materials and methods: A total of 48 Sprague-Dawley (SD) rats were randomly divided into four groups, including: the sham-operation group (n=12), the model group (n=12), the propofol group (n=12) and the inhibitor group (n=12). The rats in the sham-operation group only received thoracotomy, without the modeling of the ischemia/reperfusion injury. The model of myocardial ischemia/reperfusion injury was established in the rats of the model group, and the rats were given normal saline for intervention. The rats in the propofol group were utilized to prepare the model of myocardial ischemia/reperfusion injury and were intervened with propofol. Meanwhile, the rats in the inhibitor group received intervention with AG490 after the establishment of myocardial ischemia/reperfusion injury model. Immunohistochemistry was applied to detect the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Western blotting was utilized to measure the relative protein expressions of phosphorylated JAK2 (p-JAK2) and p-STAT3. The messenger ribonucleic acid (mRNA) expressions of Bax and Bcl-2 were determined via quantitative Polymerase Chain Reaction (qPCR). Furthermore, cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Results: Immunohistochemistry results showed that compared with the sham-operation group, the positive expression of Bax remarkably increased (p&lt;0.05), while Bcl-2 notably decreased (p&lt;0.05) in the model group, propofol group, and inhibitor group. The propofol group and inhibitor group showed a significant lower positive expression of Bax (p&lt;0.05) and evident higher positive expression of Bcl-2 (p&lt;0.05) when compared with the model group. However, there were no significant differences in the positive expressions of Bax and Bcl-2 between the propofol group and inhibitor group (p&gt;0.05). According to the results of Western blotting, the relative protein expression levels of p-JAK2 and p-STAT3 proteins were remarkably elevated in the model group, propofol group and inhibitor group in comparison with those in the sham-operation group (p&lt;0.05). Propofol group and inhibitor group exhibited remarkably lower protein expression levels of p-JAK2 and p-STAT3 compared with the model group (p&lt;0.05). However, no significant differences were observed in the protein expressions of p-JAK2 and p-STAT3 between propofol group and inhibitor group (p&gt;0.05). The results of qPCR manifested that the mRNA expression of Bax was notably higher (p&lt;0.05), whereas Bcl-2 was significantly lower (p&lt;0.05) in the model group, propofol group and inhibitor group than those of the sham-operation group. Compared with the model group, the mRNA expression of Bax was evidently declined (p&lt;0.05), while Bcl-2 was significantly elevated (p&lt;0.05) in the propofol group and inhibitor group. Meanwhile, there were no evident differences in the mRNA expressions of Bax and Bcl-2 between the propofol group and inhibitor group (p&gt;0.05). Subsequent TUNEL assay indicated that the model group, propofol group, and inhibitor group showed remarkably higher apoptosis rate than the sham-operation group (p&lt;0.05). Moreover, the apoptosis rate was remarkably reduced in the propofol group and inhibitor group in comparison with the model group (p&lt;0.05). However, no significant difference was observed in the apoptosis rate between propofol group and inhibitor group (p&gt;0.05). Conclusions: Propofol inhibits myocardial cell apoptosis after myocardial ischemia/reperfusion injury by repressing the JAK/STAT signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 3 appears to include a repeated image, although with different coloring, see red boxes. *** ![file] , 
 DOI: 10.4161 2162402X.2014.974382 u201cIn the published version of Figure 3, Author inadvertently duplicated the ANCT panels (fourth row (sic) of the images) for benign and stage II tumors during figure assembly. This error has been corrected by replacing the ANCT panel for the benign tissue in the upper right corner of the figure. The corrected Figure 3 is enclosed. The figure legend is correct as published and is shown for reference below. This error has no impact on the interpretation of the results, nor does it influence the conclusions of the work. Author apologize for any inconvenience that may have been caused. Figure 3 Validation of SPAG9 protein expression in various stages of SGT by immunohistochemistry. First panel shows representative images for H E staining in benign, malignant stage I, II, III, and IV tumor specimens. Second panel shows the representative images for the cytoplasmic localization of SPAG9 protein probed with anti-SPAG9 antibody as depicted by brown color immunoreactivity. No immunoreactivity was observed in serial tumor sections probed with control IgG, as shown in the third panel. Fourth panel depicts no immunoreactivity against SPAG9 protein in ANCT specimens when probed with anti-SPAG9 antibody. Original magnification: x400; objective: x40.u201d These were duplicated images in the fourth column, not row. ![file] , 
 Unfortunately there are repeated images between the corrected Figure 3 (below left) and Figure 4. Three are repeated by my count, but perhaps the authors could check. Apologies Iu2019ve misunderstood. *** ![file] , 
 Using ImageTwin tool, here are the overlaps or repetitions identified within and among Figures 2, 3 (corrected), 4, and 6. *** Figure 2 ![file] *** Figure 3 (corrected) ![file] *** Figure 4 ![file] *** Figure 6 ![file] ,