A mouse model of sepsis-associated DIC induced by Kappa-carrageenan and Lipopolysaccharides: Establishment and characteristics

Abstract

Background

No animal models fully replicate the pathogenesis and clinical features of sepsis-associated disseminated intravascular coagulation (DIC), which hinders mechanistic understanding and treatment development. Kappa-carrageenan (KCG) and lipopolysaccharides (LPS) induce thrombosis and systemic inflammation in mice, respectively. The combination of LPS and KCG serves as a promising method to establish a mouse model of sepsis-associated DIC.

Objective

This study aimed to establish a standardized mouse model of sepsis-associated DIC using KCG and LPS.

Methods

Kunming (KM) mice were intraperitoneally injected with KCG (25–200 mg/kg) alone or in combination with LPS (50–1250 μg/kg) to determine optimal dose. The effects of ambient temperature, gender and mouse strains on the mouse model were evaluated. Time-dependent changes in the model was examined.

Results

The combined injection of KCG (100 mg/kg) and LPS (50 μg/kg) effectively induced tail thrombosis and prolonged partial thromboplastin time (APTT). Mice housed at 16 ± 1℃ exhibited more severe thrombosis and hypocoagulability than those at 24 ± 1℃. Male and female mice exhibited similar responses. Time-course analysis revealed inflammation and blood hypocoagulability beginning from 1.5 to 24 h, with fibrinolysis inhibition occurring within 1 h. Tail thrombosis and auricle petechial developed at 3 and 6 h, respectively, and stabilized by 12 h. Thrombi in the tail, lung and liver along with organ dysfunction were obeserved at 12 h. KM and BALB/c mice exhibited longer tail thrombi than Institute of Cancer Research (ICR) mice. KM mice showed more severe blood hypocoagulability than ICR and BALB/c mice.

Conclusions

This study establishes a standardized mouse model of sepsis-associated DIC using KCG and LPS, which more accurately replicates the key clinical and pathological characteristics of sepsis-associated DIC compared to existing models. This model serves as a novelty and valuable tool for investigating the mechanisms of sepsis-associated DIC and therapeutic evaluation.