Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway

Abstract Objective We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO). Materials and methods Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg...

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Main Authors: Qing Yang, Dan Dan Huang, Da Guang Li, Bo Chen, Ling Min Zhang, Cui Ling Yuan, Hong Hong Huang
Format: Article
Language:English
Published: BMC 2019-02-01
Series:Cellular & Molecular Biology Letters
Subjects:
Online Access:http://link.springer.com/article/10.1186/s11658-019-0141-5
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author Qing Yang
Dan Dan Huang
Da Guang Li
Bo Chen
Ling Min Zhang
Cui Ling Yuan
Hong Hong Huang
author_facet Qing Yang
Dan Dan Huang
Da Guang Li
Bo Chen
Ling Min Zhang
Cui Ling Yuan
Hong Hong Huang
author_sort Qing Yang
collection DOAJ
description Abstract Objective We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO). Materials and methods Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg) and ISO + TMP (20 mg/kg). The rats in the three ISO + groups were pretreated with propranolol or TMP, while the rats in the control and ISO groups were pretreated with an equal volume of saline. Afterwards, the rats in the four administration groups were subcutaneously injected with ISO for two consecutive days. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the serum were measured using ELISA. The expressions of B-cell lymphoma-associated X-2 (Bax-2), B-cell lymphoma-2 (Bcl-2), phosphoinositide-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK-3β), MDA5 and SOD1 were determined using western blotting assay. The phosphorylation of PI3K, Akt and GSK-3β were also determined using western blotting assay. The left ventricles of the rats were extracted and stained using hematoxylin and eosin (H&E). The ST segment was recorded using electrocardiograms (ECGs). Results Administration of TMP (10, 20 mg/kg) reduced the levels of MDA and CK and the activities of SOD and LDH in the serum. Pretreatment with TMP significantly reduced the levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Treatment with TMP also improved the histopathological alteration and decreased the ST elevation. Furthermore, TMP ameliorated the expressions of Cu, SOD1, MDA5, Bax-2, Bcl-2, p-PI3K, p-Akt and p-GSK-3β in ISO-induced rats. Conclusions Tetramethylpyrazine protected against injury due to AMI by regulating the PI3K/Akt /GSK-3β signaling pathway.
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spelling doaj.art-cd12f046148341fda876abc34e5102322022-12-21T22:44:05ZengBMCCellular & Molecular Biology Letters1425-81531689-13922019-02-0124111210.1186/s11658-019-0141-5Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathwayQing Yang0Dan Dan Huang1Da Guang Li2Bo Chen3Ling Min Zhang4Cui Ling Yuan5Hong Hong Huang6Blood Transfusion Department, First Hospital of Jilin UniversityPreclinical School of North Sichuan Medical CollegeBlood Transfusion Department, First Hospital of Jilin UniversityBlood Transfusion Department, First Hospital of Jilin UniversityBlood Transfusion Department, First Hospital of Jilin UniversityBlood Transfusion Department, First Hospital of Jilin UniversityFaculty of Chinese Medical Science, Guangxi University of Chinese MedicineAbstract Objective We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO). Materials and methods Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg) and ISO + TMP (20 mg/kg). The rats in the three ISO + groups were pretreated with propranolol or TMP, while the rats in the control and ISO groups were pretreated with an equal volume of saline. Afterwards, the rats in the four administration groups were subcutaneously injected with ISO for two consecutive days. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the serum were measured using ELISA. The expressions of B-cell lymphoma-associated X-2 (Bax-2), B-cell lymphoma-2 (Bcl-2), phosphoinositide-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK-3β), MDA5 and SOD1 were determined using western blotting assay. The phosphorylation of PI3K, Akt and GSK-3β were also determined using western blotting assay. The left ventricles of the rats were extracted and stained using hematoxylin and eosin (H&E). The ST segment was recorded using electrocardiograms (ECGs). Results Administration of TMP (10, 20 mg/kg) reduced the levels of MDA and CK and the activities of SOD and LDH in the serum. Pretreatment with TMP significantly reduced the levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Treatment with TMP also improved the histopathological alteration and decreased the ST elevation. Furthermore, TMP ameliorated the expressions of Cu, SOD1, MDA5, Bax-2, Bcl-2, p-PI3K, p-Akt and p-GSK-3β in ISO-induced rats. Conclusions Tetramethylpyrazine protected against injury due to AMI by regulating the PI3K/Akt /GSK-3β signaling pathway.http://link.springer.com/article/10.1186/s11658-019-0141-5TetramethylpyrazineMyocardial ischemiaPI3KAktGSK-3β
spellingShingle Qing Yang
Dan Dan Huang
Da Guang Li
Bo Chen
Ling Min Zhang
Cui Ling Yuan
Hong Hong Huang
Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
Cellular & Molecular Biology Letters
Tetramethylpyrazine
Myocardial ischemia
PI3K
Akt
GSK-3β
title Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
title_full Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
title_fullStr Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
title_full_unstemmed Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
title_short Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway
title_sort tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the pi3k akt gsk 3β signaling pathway
topic Tetramethylpyrazine
Myocardial ischemia
PI3K
Akt
GSK-3β
url http://link.springer.com/article/10.1186/s11658-019-0141-5
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