Effects of butylphthalide on oxidative stress and inflammatory response in rats with myocardial infarction through Akt/Nrf2 signaling pathway
Authors: G-X Jiang
C-L Pan
Y-M Zhang
M Bai
Z Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: butylphthalide; oxidative stress; inflammatory response; myocardial infarction; protein kinase B
Affiliations: Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, China. .

Abstract:  Objective: The aim of this study was to investigate the effects of butylphthalide on oxidative stress and inflammatory response in rats with myocardial infarction through the protein kinase B/nuclear factor E2-related factor 2 (Akt/Nrf2) signaling pathway. Materials and methods: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including sham group (n=12), model group (n=12) and butylphthalide group (n=12). In the sham group, the heart was exposed, and normal saline was intraperitoneally injected after the operation. In the model group, acute myocardial infarction (AMI) model was established, and normal saline was intraperitoneally injected after the operation. In the butylphthalide group, AMI model was established, and butylphthalide was intraperitoneally injected after the operation. After intervention for 4 weeks, the rats were killed, and the samples were collected. The morphology of heart tissues was observed via hematoxylin-eosin (HE) staining. The expression of nicotinamide adenine dinucleotide phosphate oxidase-1 (NOX-1) was detected via immunohistochemistry. The protein expressions of phosphorylated Akt (p-Akt) and p-Nrf2 were detected via Western blotting. Moreover, the content of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was detected via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) expression levels of IL-1β, TNF-α and NOX-1 were detected via quantitative Polymerase Chain reaction (qPCR). Furthermore, the apoptosis rate of the cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Results: The morphology of heart tissues was significantly damaged in the model group and butylphthalide group compared with the sham group. However, it was significantly improved in the butylphthalide group when compared with the model group. The expression level of NOX-1 increased markedly in the model group and butylphthalide group compared with the sham group (p&lt;0.05). However, it was remarkably reduced in the butylphthalide group compared with the model group (p&lt;0.05). Meanwhile, the protein expression levels of p-Akt and p-Nrf2 were significantly higher in the model group and butylphthalide group than those of the sham group (p&lt;0.05). However, the protein expression levels of p-Akt and p-Nrf2 in the butylphthalide group were remarkably lower than the model group (p&lt;0.05). The mRNA expression levels of IL-1β, TNF-α and NOX-1 were markedly higher in the model group and butylphthalide group than those of the sham group (p&lt;0.05). However, they remarkably declined in the butylphthalide group compared with the model group (p&lt;0.05). In addition, the content of IL-1β and TNF-α increased in the model group and butylphthalide group when compared with the sham group (p&lt;0.05). The content of IL-1β and TNF-α in the butylphthalide group was significantly lower than the model group (p&lt;0.05). Furthermore, the apoptosis rate was significantly higher in the model group and butylphthalide group than the sham group (p&lt;0.05), which was significantly lower in the butylphthalide group than the model group (p&lt;0.05). Conclusions: Butylphthalide inhibits inflammatory and oxidative stress responses after AMI by regulating the Akt/Nrf2 signaling pathway, thereby inhibiting myocardial apoptosis and benefiting the morphological repair of myocardial tissues. 

Retracted: No

PubPeer comments:
 Figure 1.  Morphology of heart tissues via HE staining . ![file] Sham and Butlphthalide panels overlap with Sham and Model panels in work by other authors. Fig 1 from [Bian et al (2019)] :  Morphology of heart tissues observed via HE staining . ![file] , 
 Lower left: Figure 4.  Related protein expressions detected via Western blotting. Upper left: Figure 4 from [Rong et al (2020)] .  Expressions of related proteins detected via Western blotting . Loading controls are unexpectedly similar after some vertical stretching. ![file] Affiliations of other bands become clearer after 180-deg rotation: ![file] Clockwise from upper left: Figure 3 from [Sun et al (2019)] .  NF-u03baB protein expression determined through Western blotting ; Fig 3 from [Long et al (2019)] ; Fig 4 from [Lou et al (2019)] ; and Figure 5 from [Pan et al (2019)] . ![] , 
 #1 More overlaps - please compare Fig 1 ... ![file] with Fig 1 from [Qu et al (2019)] ,  Morphological differences of myocardial cells in rats of each group . ![file] , 
 #3 Fig 1 again. ![file] Fig 1(a) from  Sodium Ferulate Protects against Angiotensin II-Induced Cardiac Hypertrophy in Mice by Regulating the MAPK ERK and JNK Pathways ([Hu et al 2016] ). ![file] ,