Butorphanol protects on myocardial ischemia/reperfusion injury in rats through MAPK signaling pathway
Authors: M Sun
W-F He
J-L Wang
H Wang
H-W Ren
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: butorphanol; myocardial ischemia/reperfusion injury; mitogen-activated protein kinase signaling pathway; Sprague-Dawley rats; liver function indicators
Affiliations: Department of Anesthesiology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China. .

Abstract:  Objective: To explore the influence of butorphanol on myocardial ischemia/reperfusion (I/R) injury in rats through the mitogen-activated protein kinase (MAPK) signaling pathway. Materials and methods: The I/R model in Sprague-Dawley rats was established. The rats were randomly divided into normal group (n=20), myocardial I/R model group (model group, n=20), and butorphanol treatment group (treatment group, n=20). Next, the liver function indicators such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), and the myocardial function index creatine kinase (CK) in rats were detected. ELISA was carried out to measure the relative levels of tumor necrosis factor-gamma (TNF-γ), interleukin-6 (IL-6), and IL-1α in serum samples of rats. The cardiac function indexes were examined via magnetic resonance imaging (MRI) and echocardiography (ECG). Besides, the pathological changes of the myocardial tissues were detected through hematoxylin-eosin (HE) staining. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were performed to measure the mRNA and protein expression levels of the relative genes in the MAPK signaling pathway in the rat myocardial tissues. Results: The serum levels of ALP, ALT, and CK in I/R model group were significantly higher than those in the normal group. In I/R model group, the relative levels of TNF-γ, IL-6, and IL-1α, as well as left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd), were remarkably higher, while the fractional shortening (FS, %) and the ejection fraction (EF, %) were lower in comparison with those in the normal group. The HE staining results showed that the myocardial tissues in the I/R model group exhibited severe injury. The expression levels of Caspase3, MAPK, and c-Jun N-terminal kinase (JNK) were clearly higher in the I/R model group than those in the treatment group (p&lt;0.05), while the expression level of extracellular regulated protein kinase 1 (ERK1) was remarkably lower (p&lt;0.05). The protein level of MAPK in the treatment group was overtly reduced compared with that in the I/R model group (p&lt;0.05). Conclusions: Butorphanol can modulate the recovery of the myocardial injury in the rats after the myocardial I/R by inhibiting the MAPK signaling pathway. 

Retracted: No

PubPeer comments:
  Figure 3. HE staining results of rat heart. A, Model group (u00d710). B, Treatment group (u00d710). Disorderly-arranged myocardial cells and thickened muscle fibers are detected in the model group, while almost no myocardial injury is found in the treatment group. ![file] The Model image has previously appeared as  Figure 2: HE staining of heart. A, MALAT1 group in [Fan eta l (2019)] ; ![] And as the SHR group in Figure 3 of [Shi et al (2019)] ,  Pathological changes in myocardial tissues of rats in each group detected via HE staining . ![] , 
 Because these papers all have at least one image in common, while not sharing any authors or affiliations, they appear to be produced by a paper mill, which might have supplied the papers and the figures. As of today, this set contains at least 9 papers, all connected to each other with at least one photo, as per the work of Hoya Camphorifolia. * H. Wang et al. - DOI: 10.26355 eurrev_201912_19695 - https: pubpeer.com publications 7BB185FB656F0F8214F92EDFE047FF * HT Zeng et al. - DOI: 10.26355 eurrev_201908_18757 - https: pubpeer.com publications B226E56465DACEA93791215756340B * MH Lun et al. - DOI: 10.26355 eurrev_202005_21366 - https: pubpeer.com publications AAA8F559D37A6D853CC16764A06A53 * Q Xu et al. - DOI: 10.26355 eurrev_201909_19026 - https: pubpeer.com publications C6F5DA3CA8F64BD57CE8A9B38616D0 * YJ Shi et al. - DOI: 10.26355 eurrev_201906_18082 - https: pubpeer.com publications 153695342827B732C15C614F61DF10 * YJ Wan et al. - DOI: 10.26355 eurrev_201908_18622 - https: pubpeer.com publications 41C0C61998A1A6C6339689A61A6ABF * YT Zhu et al. - DOI: 10.26355 eurrev_202005_21205 - https: pubpeer.com publications 277C24C645B71AF55A72A1200C46B4 * YY Wang et al. - DOI: 10.26355 eurrev_201912_19696 - https: pubpeer.com publications 702E90DEA6ED9278B2F67828C5329D * YZ Fan et al. - DOI: 10.26355 eurrev_201910_19306 - https: pubpeer.com publications 0B80BCE778E3D360504102D662CDE5 , 
 In addition to the findings above, the b-actin panel in Figure 5 of this paper looks very similar to GAPDH panels in MH Lun and YJ Wan et al. (see DOIs in remark #2). Figure 5 of H Wang et al: ![file] Figure 3 of MH Lun et al: ![file] Figure 4 of YJ Wan et al: ![file] ,