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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Shenfu injection attenuates cardiac dysfunction and inhibits apoptosis in septic mice
Liyun Zhao1, Lili Jin2, Yuanyuan Luo3
1Department of Critical Care Medicine, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, China.
Insights
Shenfu injection reduces mortality and prevents cardiac dysfunction in sepsis. It protects the heart by decreasing inflammation and apoptosis via the AKT/GSK-3β pathway.
Area of Science:
- Cardiology
- Pharmacology
- Immunology
Background:
- Sepsis and septic shock often lead to cardiac dysfunction and multiple organ failure.
- Shenfu injection, a traditional Chinese medicine, shows potential cardio-protective effects.
- The precise role and mechanism of Shenfu injection in sepsis-induced myocardial dysfunction are not fully understood.
Purpose of the Study:
- To investigate the efficacy of Shenfu injection in alleviating myocardial injury during sepsis.
- To elucidate the underlying mechanisms of Shenfu injection's cardio-protective effects in a sepsis model.
Main Methods:
- A sepsis model was established in C57BL/6 mice using cecal ligation and puncture (CLP).
- Cardiac function, inflammatory markers, and myocyte apoptosis were assessed.
- The study evaluated the impact of Shenfu injection on mortality, cardiac performance, inflammatory cytokine levels, apoptosis, and key signaling pathways (NF-κB, AKT/GSK-3β).
Main Results:
- CLP surgery significantly reduced survival and left ventricular function compared to sham procedures.
- Shenfu injection treatment lowered mortality and preserved left ventricular function in septic mice.
- Shenfu injection decreased myocardial inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1), reduced apoptotic myocardiocyte death, suppressed NF-κB activation, and prevented decreases in myocardial phospho-Akt and phospho-GSK-3β.
Conclusions:
- Shenfu injection attenuates cardiac dysfunction and inflammatory injury in sepsis.
- It protects against myocardiocyte apoptosis during sepsis.
- The protective effects are mediated through the activation of the AKT/GSK-3β signaling pathway.
Background:
Cardiac dysfunction frequently occurs after sepsis and septic shock and contributes to multiple organ failure. Shenfu injection, a well-known Chinese medicine formulation, has recently been demonstrated to possess potential cardio-protective effects, although its effect and mechanism in sepsis-induced myocardial dysfunction remains unclear.
Methods:
To investigate whether Shenfu injection could alleviate myocardial injury and improve cardiac function, a model of sepsis was induced by cecal ligation and puncture (CLP) surgery in C57BL/6 mice. Cardiac function, inflammatory factors, and apoptosis were evaluated in the myocardium.
Results:
Our results showed that the survival and left ventricular function markedly declined when exposed to CLP compared with the sham procedure. In contrast, Shenfu injection lowered mortality and prevented CLP from triggering left ventricular dysfunction. Moreover, mice treated with Shenfu injection exhibited noticeably decreased myocardial inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocytechemoattractantprotein-1 (MCP-1)] and reduced apoptotic myocardiocytes death compared with mice that had CLP. The activation of myocardial NF-кB detected in septic mice was suppressed by the presence of Shenfu injection, as evidenced by decreased nuclear translocation of the NF-кB p65 subunit. Moreover, Shenfu injection also prevented sepsis-caused decreases in myocardial phospho-Akt and phospho-GSK-3β in septic mice.
Conclusions:
These data suggest that administration of Shenfu injection attenuates cardiac dysfunction, protects against inflammatory injury, and reduces apoptosis of myocardiocytes during sepsis by activating the AKT/GSK-3β pathway.
