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Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction.
Yang, Chun; Xia, Wan; Liu, Xiaolin; Lin, Jian; Wu, Aiping.
Afiliação
  • Yang C; Department of Emergency Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
  • Xia W; Department of Rehabilitation Medicine, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
  • Liu X; Department of Rehabilitation Medicine, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
  • Lin J; Department of Rehabilitation Medicine, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
  • Wu A; Department of Rehabilitation Medicine, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China.
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.
Assuntos

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 / Cardiopatias / Miocárdio Limite: Animals Idioma: En Revista: Int J Mol Med Ano de publicação: 2019 Tipo de documento: Article

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 / Cardiopatias / Miocárdio Limite: Animals Idioma: En Revista: Int J Mol Med Ano de publicação: 2019 Tipo de documento: Article