Articles: sepsis.
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Pulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α 2 -adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α 2A -AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. ⋯ Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α 2 -AR. Blockage of α 2 -AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway.
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Enteral nutrition is the key therapy in septic patients. Different formulas of enteral nutrition have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of enteral nutrition supplemented with octanoic acid on lipopolysaccharide-induced intestinal injury and explored the potential mechanism. ⋯ Enteral nutrition supplemented with octanoic acid prevents lipopolysaccharide-induced intestinal injury via the peroxisome proliferator-activated receptor γ/STAT-1/myeloid differentiation factor 88 pathway.
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Background : We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods : A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. ⋯ In addition, geniposide elevated the PPARγ level in monocytes ( P < 0.05). Conclusions : High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.
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Etomidate is an anesthetic agent used in hemodynamically unstable patients, but its use has been controversial in septic patients. The response of high-mobility group box 1 (HMGB1), a late-phase lethal cytokine in sepsis, to etomidate has not been reported. This study investigated the effects of etomidate on the expression and release of HMGB1 and the underlying mechanism using a cecal ligation and puncture (CLP) model. ⋯ Immunohistochemical staining also revealed that etomidate treatment inhibited HMGB1 expression. Etomidate inhibited the systemic release of HMGB1 and its expression in various organs. The mechanism may be associated with the inhibitory effects of etomidate on pro-inflammatory cytokine release and NF-ĸB activity.