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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Klotho alleviates sepsis-associated myocardial inflammation and apoptosis
Zhongcheng Wei1, Juan Liu2, Hailang Liu1
1Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu, China.
Insights
Klotho (KL) protects the heart during sepsis. This study shows that increasing KL levels can improve cardiac function by reducing inflammation and apoptosis in sepsis-associated cardiac dysfunction.
Area of Science:
- Cardiology
- Molecular Biology
- Pathology
Background:
- Klotho (KL) is a protein known to protect against various pathological conditions.
- Sepsis can lead to severe cardiac dysfunction, a major cause of mortality.
- The role of Klotho in sepsis-induced cardiac dysfunction requires further investigation.
Purpose of the Study:
- To investigate the effect of Klotho (KL) on sepsis-associated cardiac dysfunction.
- To determine if KL modulates cardiac dysfunction by affecting oxidative stress and apoptosis.
- To explore the therapeutic potential of KL in sepsis.
Main Methods:
- A mouse model of sepsis was induced using lipopolysaccharide (LPS) administration.
- Klotho knockout (KO) and overexpression models were used to study KL's role.
- Cardiac function, inflammatory factors (TNF-α, IL-1β, IL-6), and apoptosis biomarkers (Bcl2, Bax) were assessed.
Main Results:
- Klotho expression was reduced in the hearts of septic mice.
- Cardiac dysfunction worsened with KL deficiency and improved with KL upregulation.
- LPS treatment increased inflammatory factors and apoptosis markers, effects exacerbated by KL deficiency and ameliorated by KL overexpression.
Conclusions:
- Klotho plays a crucial role in regulating sepsis-induced cardiac dysfunction.
- KL alleviates cardiac dysfunction by reducing inflammation and apoptosis.
- Upregulating Klotho may represent a future therapeutic strategy for sepsis patients with cardiac dysfunction.
Abstract:
Klotho (KL) protects against various pathological phenotypes. The present study was designed to investigate the effect of KL on sepsis-associated cardiac dysfunction, and whether KL modulated sepsis-associated cardiac dysfunction via oxidative stress and apoptosis. Experiments were carried out in mice treated with lipopolysaccharide (LPS) to induce the septic model. The expression of KL was reduced in the heart of septic mice induced by LPS administration. The cardiac dysfunction of septic mice was deteriorated after KL KO, and was alleviated by KL upregulation. The inflammatory factors of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 were increased in the heart after LPS treatment, and these increases were further enhanced in KL deficiency mice, and were alleviated in KL overexpressed mice. The apoptosis biomarkers of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) levels were changed in the heart of septic mice, which were exacerbated by KL KO and were ameliorated by KL overexpression. These results indicated that KL involved in the regulation of sepsis-induced cardiac dysfunction via alleviating inflammation and apoptosis. Upregulation KL may be a therapeutic strategy to improve cardiac function in septic patients in the future.
