Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia-reperfusion injury through inhibition of miR-146a-5p expression.

Abstract

The aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia-reperfusion (I/R) injury. Hypoxia/reoxygenation (H/R) model in neonatal rat cardiomyocytes, and I/R model in rats, were established following troxerutin preconditioning. The quantitative real-time polymerase chain reaction analysis was performed to examine the messenger RNA miR-146a-5p expression in cardiomyocytes and myocardial tissues. Hemodynamic parameters and serum creatine kinase, lactate dehydrogenase, tumor necrosis factor-α, and interleukin-10 were evaluated. Infarct size was examined by 2,3,5-triphenyltetrazolium chloride staining. Besides, myocardial apoptosis was detected by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the protein levels of caspase-3, Bax, and Bcl-2. The results showed that, troxerutin decreased rat cardiomyocyte apoptosis during H/R injury. Furthermore, the antiapoptotic effect of troxerutin against I/R injury was mediated by miR-146a-5p downregulation. In vivo experiments suggested that troxerutin alleviated myocardial I/R injury in rats via inhibition of miR-146a-5p. In conclusion, troxerutin exerted cardioprotective effects during I/R injury by downregulating miR-146a-5p.

• Authors: Liliang Shu, Wanzhe Zhang, Gongcheng Huang, Chen Huang, Xiaohua Zhu, Gang Su, Jing Xu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 6 Pg. 9274-9282 (06 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30417352 (Publication Type: Journal Article)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Hydroxyethylrutoside
• MIRN146 microRNA, rat
• MicroRNAs
• troxerutin
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects, genetics)
• Down-Regulation (drug effects)
• Gene Expression Regulation (drug effects)
• Hemodynamics (drug effects)
• Hydroxyethylrutoside (analogs & derivatives, pharmacology)
• Male
• MicroRNAs (genetics, metabolism)
• Myocardial Reperfusion Injury (genetics, pathology, physiopathology)
• Myocardium (pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Wistar