Roles of apoptosis and inflammation in a rat model of acute lung injury induced right ventricular dysfunction
Copyright © 2018 Elsevier Masson SAS. All rights reserved..
AIM: The effect of intratracheal lipopolysaccharide (LPS) instillation on right ventricular dysfunction in rats was studied with the aim of exploring underlying mechanisms.
MAIN METHODS: A single dose of LPS (10 mg/kg) or an equal volume of saline was instilled intratracheally and lung injury evaluated using histopathologic scoring and wet/dry (W/D) weight ratio at 6 or 12 h post-administration. Besides, serum atrial natriuretic peptide (ANP) was detected using an enzyme-linked immunosorbent assay (ELISA) and right ventricle β-myosin heavy chain (β-MHC) presence was examined using reverse transcription polymerase chain reaction (RT-PCR). Echocardiography examined pulmonary artery acceleration time (PAAT), right ventricular free wall thickness (RVFWT), tricuspid annular plane systolic excursion (TAPSE), and right ventricular end-diastolic diameter (RVEDD). In addition, right ventricular TUNEL staining and Western blots of Bax and Bcl-2 were performed. Right ventricle and left ventricle caspases-3, -8, and -9 activity were examined using fluorometric assay. Finally, right ventricle myeloperoxidase (MPO) neutrophil staining, and right ventricle and plasma cytokines TNF-α, IL-1β, IL-6 detection was performed.
KEY FINDINGS: Histopathologic lung injury and increased W/D weight ratio was seen at 6 h after LPS intratracheal instillation, along with increased ANP, but not β-MHC. Pulmonary hypertension was indicated by decreased PAAT at 6 h post-exposure. Right ventricular systolic dysfunction and dilation were observed at 12 h post-exposure, as indicated by a significant decrease of TAPSE and increase of RVEDD. Of note, the procedure led to an increased right ventricle TUNEL positive cardiomyocytes, an increased Bax/Bcl-2 ratio, and increased right and left ventricle caspases-3, -8, and -9 activity as early as 6 h post-exposure, which was paralleled by increased right ventricle MPO staining and increased expression of right ventricle and serum cytokines TNF-α, IL-1β, and IL-6.
SIGNIFICANCE: As well as acute lung injury, a single dose of LPS intratracheally instilled can induce pulmonary hypertension at 6 h post-exposure, with obvious right ventricular systolic dysfunction and right ventricular dilation present at 12 h post-exposure, possibly via cardiomyocytes apoptosis and inflammation.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2018 |
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Erschienen: |
2018 |
Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 108(2018) vom: 01. Dez., Seite 1105-1114 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ma, Shaolei [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 18.03.2019 Date Revised 18.03.2019 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.biopha.2018.09.115 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM29006547X |
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520 | |a Copyright © 2018 Elsevier Masson SAS. All rights reserved. | ||
520 | |a AIM: The effect of intratracheal lipopolysaccharide (LPS) instillation on right ventricular dysfunction in rats was studied with the aim of exploring underlying mechanisms | ||
520 | |a MAIN METHODS: A single dose of LPS (10 mg/kg) or an equal volume of saline was instilled intratracheally and lung injury evaluated using histopathologic scoring and wet/dry (W/D) weight ratio at 6 or 12 h post-administration. Besides, serum atrial natriuretic peptide (ANP) was detected using an enzyme-linked immunosorbent assay (ELISA) and right ventricle β-myosin heavy chain (β-MHC) presence was examined using reverse transcription polymerase chain reaction (RT-PCR). Echocardiography examined pulmonary artery acceleration time (PAAT), right ventricular free wall thickness (RVFWT), tricuspid annular plane systolic excursion (TAPSE), and right ventricular end-diastolic diameter (RVEDD). In addition, right ventricular TUNEL staining and Western blots of Bax and Bcl-2 were performed. Right ventricle and left ventricle caspases-3, -8, and -9 activity were examined using fluorometric assay. Finally, right ventricle myeloperoxidase (MPO) neutrophil staining, and right ventricle and plasma cytokines TNF-α, IL-1β, IL-6 detection was performed | ||
520 | |a KEY FINDINGS: Histopathologic lung injury and increased W/D weight ratio was seen at 6 h after LPS intratracheal instillation, along with increased ANP, but not β-MHC. Pulmonary hypertension was indicated by decreased PAAT at 6 h post-exposure. Right ventricular systolic dysfunction and dilation were observed at 12 h post-exposure, as indicated by a significant decrease of TAPSE and increase of RVEDD. Of note, the procedure led to an increased right ventricle TUNEL positive cardiomyocytes, an increased Bax/Bcl-2 ratio, and increased right and left ventricle caspases-3, -8, and -9 activity as early as 6 h post-exposure, which was paralleled by increased right ventricle MPO staining and increased expression of right ventricle and serum cytokines TNF-α, IL-1β, and IL-6 | ||
520 | |a SIGNIFICANCE: As well as acute lung injury, a single dose of LPS intratracheally instilled can induce pulmonary hypertension at 6 h post-exposure, with obvious right ventricular systolic dysfunction and right ventricular dilation present at 12 h post-exposure, possibly via cardiomyocytes apoptosis and inflammation | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Acute lung injury | |
650 | 4 | |a Apoptosis | |
650 | 4 | |a Echocardiography | |
650 | 4 | |a Inflammation | |
650 | 4 | |a LPS | |
650 | 4 | |a Right ventricular dysfunction | |
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700 | 1 | |a Cao, Quan |e verfasserin |4 aut | |
700 | 1 | |a Zuo, Xiangrong |e verfasserin |4 aut | |
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