Ulinastatin improves myocardial ischemia-reperfusion injury in rats through endoplasmic reticulum stress-induced apoptosis pathway
Authors: M-H Lun
W Du
Z Cai
Z-Q Huang
X-Y Jin
M-Y Wang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ulinastatin; myocardial ischemia-reperfusion injury; endoplasmic reticulum stress; apoptosis pathway; rats
Affiliations: Department of Anesthesiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China. .

Abstract:  Objective: To investigate the protective role of ulinastatin (UTI) on myocardial ischemia-reperfusion (I/R) injury in rats via endoplasmic reticulum stress (ERS)-induced apoptosis pathway. Materials and methods: A total of 60 rats were randomly divided into normal group (n=20), myocardial I/R model group (model group, n=20), and myocardial I/R model+UTI treatment group (treatment group, n=20). The myocardial function indicators [creatinine (Scr) and creatine kinase (CK)] were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to measure serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). Meanwhile, the contents of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in rat left ventricular tissues were determined by ELISA as well. The cardiac function indexes were determined via magnetic resonance imaging (MRI) and echocardiography (ECG). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining assay was carried out to detect the apoptosis of myocardial tissues. Additionally, the expression levels of endoplasmic reticulum stress and apoptosis genes were measured through quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assay and Western blotting analysis, respectively. Results: Serum levels of alanine aminotransferase (ALT), CK, and Scr in model group were significantly higher than those in normal group (p&lt;0.05). Besides, rats in model group had significantly lowered SOD, ejection fraction (EF, %), and fractional shortening (FS, %) than those in normal group (p&lt;0.05). In addition, remarkably increased contents of TNF-α, IL-6, MMP-9, MDA, and ROS, as well as higher left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) were observed in model group in comparison with normal group (p&lt;0.05). TUNEL staining results revealed that there were more apoptotic cells in model group than that in the other two groups (p&lt;0.05). Expression levels of cysteine aspartic acid-specific protease 12 (Caspase-12) and glucose-regulated protein 78 (GRP78) were evidently higher in model group than those in normal group (p&lt;0.05), while the expression level of B-cell lymphoma 2 (Bcl-2) was clearly lower in model group than that in normal group (p&lt;0.05). UTI treatment partially reversed the above expression changes (p&lt;0.05). Conclusions: UTI has a protective effect against myocardial I/R injury in rats by repressing the occurrence of ERS-induced apoptosis. 

Retracted: No

PubPeer comments:
 Fig 1: ![file] Compare Normal panel with Control panel of Fig 4 from [Zhu et al (2020)] . ![] , 
 Figure 3: The GAPDH panel in this paper looks very similar to that seen in Figure 4 of YJ Wan et al., DOI: 10.26355 eurrev_201908_18622 . The two papers have no authors, institutions, or even tissue samples in common. Figure 3 here shows heart tissue, while that in YJ Wan shows retinal (eye) tissue. YJ Wan, Figure 4: ![file] MH Lun, Figure 3: ![file] A closeup of the GAPHD panel as shown in YJ Wan (eye tissue, left) and in MH Lun (heart tissue, right): ![file] , 
 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 The paper by H. Wang also contains the Western blot mentioned above. , 
 #2 *[left]* Fig 3. *[right]* Fig 4a from  Influence of miRNA-30a-5p on Pulmonary Fibrosis in Mice with Streptococcus pneumoniae Infection through Regulation of Autophagy by Beclin-1 ([Liu et al 2021] ). ![file] ,