Effects of pterostilbene on myocardial function, myocardial fibrosis and inflammatory response in rats with acute myocardial infarction and on Notch1/eIF3a signaling pathway
10.12092/j.issn.1009-2501.2020.05.003
- VernacularTitle: 紫檀芪对急性心肌梗死大鼠心肌功能,心肌纤维化和炎症反应的作用及对Notch1/eIF3a信号通路的影响
- Author:
Wei ZHAO
1
Author Information
1. Wenzhou People's Hospital
- Publication Type:Journal Article
- Keywords:
Acute myocardial infarction;
Myocardial fibrosis;
Myocardial inflammatory factors;
Notch1/eIF3a signaling pathway;
Pterostilbene;
Ventricular remodeling
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(5):498-504
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To analyze the effects of pterostilbene on myocardial function, myocardial fibrosis and inflammatory response in rats with acute myocardial infarction and on Notch1/eIF3a signaling pathway. METHODS: Seventy-five Wistar male rats of SPF grade were selected and divided into 5 groups. The low-, medium-, high-dose groups of pterostilbene were pretreated with pterostilbene solution before modeling. The dosage was 10, 20 and 40 mg/kg of the pterostilbene sputum solution, rats of the model group and the normal group were intragastrically administered with the same dose of normal saline; except for the normal group, other rats were prepared with AMI model. The left ventricular function, cardiac blood flow index, myocardial histopathology and fibrosis, myocardial inflammatory factor content, eIF3a and Notch1 protein and mRNA expression were observed. RESULTS: LVFS and LVEF were lower in the model group than in the normal group. LVEDd, LVESd, LVESV and LVEDV were higher than those in the normal group. The LVFS and LVEF in the low, medium and high dose groups of the pterostilbene were higher than those in the model group, LVEDd, LVESd, LVESV, and LVEDV were lower than the model group, and the difference was statistically significant (P<0.05).In the model group, the -dp/dtmax, +dp/dtmax, and LVSP were lower than the normal group, and the LVEDP was higher than the normal group. The -dp/dtmax, +dp/dtmax, and LVSP in the low, medium, and high dose groups of the pterostilbene were increased as compared with model group; while LVEDP was lower than the model group, and the difference was statistically significant (P<0.05).The contents of IL-6, IL-1β and TNF-α in the myocardial tissue of the model group were higher than those in the normal group. The contents of IL-6, IL-1β and TNF-α in the myocardial tissue of rats with low, medium and dose groups of the pterostilbene were decreased as compared with the model group, the difference was statistically significant (P<0.05). The expression of eIF3a and Notch1 protein and mRNA in the myocardial tissue of the model group was higher than that in the normal group. eIF3a, Notch1 protein and mRNA expression in the low-, medium-, and high-dose rat myocardial tissue were lower than the model group, and the difference was statistically significant (P<0.05).CONCLUSION: The development of myocardial inflammation and fibrosis in AMI rats may be associated with the increase of eIF3a expression in the downstream of Notch signaling pathway. Pretreatment of pterostilbene can significantly improve ventricular remodeling in AMI rats, and its mechanism may be related to the inhibition of eIF3a and Notch1 expression.