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Updated: Feb 1, 2026
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Tropisetron inhibits sepsis by repressing hyper-inflammation and regulating the cardiac action potential in rat
Zhengjiang Liu1, Zhiheng Zeng2, Changdong Wu3
1Department of Cardiology, the Six Affiliated Hospital of Guangzhou Medical University/ Qingyuan People's Hospital, Qingyuan 511500, China.
Objective:
The objective of the present investigation was to explore the possible effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as well as the cardiac action potential in septic rats.
Methods:
The cecal ligation and perforation (CLP) method was utilized to construct abdominal infarction in rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for assessing survival and 28 for detecting the expression levels of IL-6 and IgE, myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after establishment of the sepsis rat model, immunohistochemistry was used to analyze 5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) was employed to monitor the serum levels of IL-6, CKMB, sST2 and IgE. Furthermore, the structure of the myocardium in various groups was examined by H&E staining.
Results:
The levels of IL-6, CK-MB, sST2 and IgE in the sepsis group were significantly higher than those of the sham group (P < 0.01). Furthermore, the heart rate in the sepsis group was lower than that of the sham group (P < 0.01), and the time of atrial ventricular action potential in the sepsis group was longer than that of the sham group (P < 0.05). In addition, immunohistochemical analyses showed that the area, intensity and index of 5-HT3 receptor in the sepsis group were significantly lower than those of the sham group (P < 0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression levels, and inductive effects on atrial ventricular action potential in the sepsis group.
Conclusions:
Sepsis leads to systemic inflammatory reaction, resulting in myocardial injury, structural changes and immune imbalance. The inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory disorder by the efferent vagus nerve may be one of the important mechanisms leading to cardiac electrophysiological changes in sepsis.
Insights
Tropisetron, a 5-HT3 receptor antagonist, reduced inflammatory factors and improved cardiac function in septic rats. This suggests tropisetron may mitigate sepsis-induced myocardial injury and electrophysiological changes.
Area of Science:
- Pharmacology
- Cardiology
- Immunology
Background:
- Sepsis triggers systemic inflammation, leading to myocardial injury and cardiac dysfunction.
- Inflammatory mediators like IL-6, CK-MB, sST2, and IgE play a crucial role in sepsis-induced cardiac damage.
- Cardiac electrophysiological changes, including altered action potentials, are observed in sepsis.
Purpose of the Study:
- To investigate the effect of tropisetron, a 5-HT3 receptor antagonist, on inflammatory markers and cardiac function in a rat model of sepsis.
- To assess tropisetron's impact on interleukin-6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2), and immunoglobulin E (IgE) levels.
- To evaluate tropisetron's influence on cardiac action potential and myocardial structure in septic rats.
Main Methods:
- A cecal ligation and perforation (CLP) model was used to induce sepsis in Sprague Dawley rats.
- Serum levels of IL-6, CK-MB, sST2, and IgE were measured using ELISA.
- Immunohistochemistry and H&E staining were employed to analyze 5-HT3 receptor expression and myocardial structure, respectively.
Main Results:
- Sepsis significantly increased IL-6, CK-MB, sST2, and IgE levels, while decreasing heart rate and prolonging atrial ventricular action potential.
- 5-HT3 receptor expression was significantly reduced in septic rats compared to controls.
- Tropisetron administration significantly inhibited the expression of IL-6, CK-MB, sST2, and IgE, and improved cardiac electrophysiological parameters.
Conclusions:
- Sepsis induces a systemic inflammatory response, myocardial injury, and immune imbalance.
- Tropisetron demonstrates significant anti-inflammatory effects and improves cardiac electrophysiological function in sepsis.
- The efferent vagus nerve's role in regulating inflammatory disorders may mediate tropisetron's beneficial effects on cardiac electrophysiology during sepsis.
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