Cargando…

Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway

OBJECTIVE: The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. METHODS: A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assi...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Xiangyang, Hu, Jing, Wang, Ya, Ye, Hongwei, Li, Xiaohong, Gao, Qin, Li, Zhenghong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196799/
https://www.ncbi.nlm.nih.gov/pubmed/30402501
http://dx.doi.org/10.1155/2018/3071959
_version_ 1783364622737211392
author Cheng, Xiangyang
Hu, Jing
Wang, Ya
Ye, Hongwei
Li, Xiaohong
Gao, Qin
Li, Zhenghong
author_facet Cheng, Xiangyang
Hu, Jing
Wang, Ya
Ye, Hongwei
Li, Xiaohong
Gao, Qin
Li, Zhenghong
author_sort Cheng, Xiangyang
collection PubMed
description OBJECTIVE: The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. METHODS: A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. CONCLUSION: The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury.
format Online
Article
Text
id pubmed-6196799
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-61967992018-11-06 Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway Cheng, Xiangyang Hu, Jing Wang, Ya Ye, Hongwei Li, Xiaohong Gao, Qin Li, Zhenghong J Diabetes Res Research Article OBJECTIVE: The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. METHODS: A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. CONCLUSION: The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury. Hindawi 2018-10-08 /pmc/articles/PMC6196799/ /pubmed/30402501 http://dx.doi.org/10.1155/2018/3071959 Text en Copyright © 2018 Xiangyang Cheng et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cheng, Xiangyang
Hu, Jing
Wang, Ya
Ye, Hongwei
Li, Xiaohong
Gao, Qin
Li, Zhenghong
Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title_full Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title_fullStr Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title_full_unstemmed Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title_short Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway
title_sort effects of dexmedetomidine postconditioning on myocardial ischemia/reperfusion injury in diabetic rats: role of the pi3k/akt-dependent signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196799/
https://www.ncbi.nlm.nih.gov/pubmed/30402501
http://dx.doi.org/10.1155/2018/3071959
work_keys_str_mv AT chengxiangyang effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT hujing effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT wangya effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT yehongwei effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT lixiaohong effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT gaoqin effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway
AT lizhenghong effectsofdexmedetomidinepostconditioningonmyocardialischemiareperfusioninjuryindiabeticratsroleofthepi3kaktdependentsignalingpathway