Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction.
Int J Mol Med
; 44(2): 417-426, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31173172
ABSTRACT
Myocardial injury is one of the main symptoms of sepsis. However, the mechanisms underlying sepsisinduced myocardial dysfunction remain unclear. In the present study, the concentration of cardiac troponin T (CTnT) in serum was measured using an enzymelinked immunosorbent assay kit. The levels of interleukin (IL)1ß and IL18 were assessed by reverse transcriptionquantitative polymerase chain reaction (RTqPCR) analysis and the level of malondialdehyde (MDA) was determined using a corresponding kit. Myocardial pathology was analyzed via hematoxylin and eosin staining. RTqPCR analysis and western blotting and/or immunohistochemistry were used to quantify the expression levels of thioredoxininteracting protein (TNXIP), NODlike receptor pyrin domain containing 3 (NLRP3), cleaved caspase1, caspase1, catalase and manganesesuperoxide dismutase (MnSOD). The viability of cells was determined using a cell counting kit8. Apoptosis and reactive oxygen species (ROS) were examined using flow cytometry. Models of sepsisinduced myocardial injury were successfully established; evidence included increases in the levels of CTnT, IL1ß, IL18 and MDA and myocardial tissue damage in vivo, and decreased cell viability and improvements in IL1ß and IL18 in vitro. The levels of TXNIP, NLRP3 and cleaved caspase1 were upregulated in the sepsis models. Small interfering RNA targeting TNXNIP (siTXNIP) increased cell viability, reduced the apoptotic rate and attenuated the release of IL1ß and IL18. The levels of TXNIP, NLRP3 and cleaved caspase1 and production of ROS were suppressed by siTXNIP, accompanied by increases in catalase and MnSOD. TXNIP/NLRP3 serves an important role in the development of sepsisinduced myocardial damage.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
Proteínas de Ciclo Celular
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
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Cardiopatias
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Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2019
Tipo de documento:
Article