Simvastatin Improves Outcomes of Endotoxin-induced Coagulopathy by Regulating Intestinal Microenvironment.
Curr Med Sci
; 42(1): 26-38, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-35041135
ABSTRACT
OBJECTIVE:
The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy, which is a strong predictor of mortality in patients with severe sepsis. Simvastatin plays an important role in reducing inflammation. In addition, the gut has long been hypothesized to be the "motor" of critical illness, driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation. Whether simvastatin plays a role in severe endotoxin-induced coagulopathy through the gut is unclear.METHODS:
In this study, mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve h later, cytokine release, coagulation dysfunction, organ damage, and survival were assessed. Besides, the intestinal barrier, permeability, bacteria abundance, and translocation were evaluated.RESULTS:
We found that the severity of endotoxin-induced coagulopathy was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition, and improved survival time. Also, simvastatin reduced epithelial apoptosis and improved intestinal barrier function by upregulating antimicrobial peptides, lysozyme, and mucins. Simvastatin increased Lactobacillales counts, while the lipopolysaccharide group showed increased Desulfovibrio and Mucispirillum, which can produce harmful toxins. Finally, the decreased intestinal permeability in the simvastatin group caused reduced bacterial translocation in the organs and blood, both in terms of quantity and species.CONCLUSION:
Simvastatin improves the prognosis of severe endotoxemia, and the intestinal microenvironment participates in this process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Transtornos da Coagulação Sanguínea
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Endotoxemia
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Sinvastatina
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Endotoxinas
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Microbioma Gastrointestinal
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Enteropatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Curr Med Sci
Ano de publicação:
2022
Tipo de documento:
Article