Dexmedetomidine alleviates cardiomyocyte apoptosis and cardiac dysfunction may be associated with inhibition of RhoA/ROCK pathway in mice with myocardial infarction.

Abstract

The global incidence of myocardial infarction has been consistently high, and it is one of the main causes of poor cardiovascular prognosis. Dexmedetomidine (DEX) is a highly selective α2 receptor agonist. Recent studies have found that DEX has a protective effect on myocardial infarction, but its specific mechanism is still unclear. In this experiment, we permanently ligated the anterior descending branch of mice to explore the protective mechanism of DEX against myocardial infarction. Our study found that intraperitoneal injection of DEX for 7 days after myocardial infarction in mice can increase the reduction of ejection fraction (EF) and fractional shortening (FS) caused by myocardial infarction and significantly reduce the release of serum markers. The results of myocardial HE and Sirius red staining suggest that the changes in the myocardial structure of mice after using DEX are reduced. Immunohistochemistry shows that DEX reduces the expression of ROCK1 protein after myocardial infarction. TUNEL staining and the protein expression levels of cleaved caspase-3 and cleaved caspase-9 were used to detect cell apoptosis and results make clear that DEX can reduce the apoptosis caused by myocardial infarction. Western blot experiments showed that DEX can reduce the expression levels of ROCK1 and ROCK2 (Rho-kinase). At the same time, it was observed that DEX improved the Bcl-2/Bax ratio. The above results indicate that DEX reduces cardiomyocyte apoptosis and improves cardiac function likely through inhibiting the RhoA/ROCK signaling pathway. This study may provide new insights into the protective effect of DEX after myocardial infarction in mice.

• Authors: Tao Sun, Qian Gong, Ying Wu, Zhiming Shen, Yan Zhang, Shenglin Ge, Jing-Si Duan
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 394 Issue 7 Pg. 1569-1577 (07 2021) ISSN: 1432-1912 [Electronic] Germany
• PMID: 33782744 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Dexmedetomidine
• rho-Associated Kinases
• RhoA protein, mouse
• rhoA GTP-Binding Protein

Topics

• Adrenergic alpha-2 Receptor Agonists (pharmacology, therapeutic use)
• Animals
• Apoptosis (drug effects, physiology)
• Dexmedetomidine (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Signal Transduction (drug effects, physiology)
• rho-Associated Kinases (antagonists & inhibitors, metabolism)
• rhoA GTP-Binding Protein (antagonists & inhibitors, metabolism)