Protective Effect of Empagliflozin and Dapagliflozin on Palmitic Acid-induced Cardiomyocytes Injury and Its Underlying Mechanism
10.13748/j.cnki.issn1007-7693.20223273
- VernacularTitle:恩格列净及达格列净对棕榈酸诱导的心肌细胞损伤的保护作用及其机制
- Author:
WEI Yudi
1
;
LUO Shenhe
1
;
JIN Honghua
2
Author Information
1. College of Pharmacy, Yanbian University, Yanji 133002, China;
2. Department of Pharmacy, Affiliated Hospital of Yanbian University, Yanji 133002, China
- Publication Type:Journal Article
- Keywords:
empagliflozin;
dapagliflozin;
palmitic acid;
cardiomyocytes
- From:
Chinese Journal of Modern Applied Pharmacy
2023;40(20):2884-2890
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the protective effect of sodium-glucose cotransporter 2 inhibitors empagliflozin (EMPA) and dapagliflozin(DAPA) on palmitic acid(PA)-induced injury of rat H9c2 cardiomyocytes and its possible mechanism. METHODS H9c2 myocardial cell injury was induced by PA. CCK-8 method was used to screen the optimal dosage of PA, EMPA and DAPA. The protein expression levels of TLR4, p-AKT, p-mTOR, Nrf2 and HO-1 were detected by Western blotting. The expressions of IL-1β, IL-6, TNF-α were detected by ELISA. ROS levels in PA-induced H9c2 cardiomyocytes were determined by fluorescence microscopy and flow cytometry. RESULTS The survival rate of H9c2 cardiomyocytes decreased significantly after treatment of PA 100 μmol·L-1 for 24 h(P<0.01), the expression of IL-1β, IL-6, TNF-α, TLR4, p-mTOR and ROS were significantly increased(P<0.01), and the protein expression of p-AKT, Nrf2 and HO-1 was significantly decreased(P<0.01). Compared with the model group, the cell survival rate was significantly increased after EMPA and DAPA treatment(P<0.01), the expression of IL-1β, IL-6, TNF-α, TLR4, p-mTOR and ROS levels were significantly decreased(P<0.05 or P<0.01), and the protein expression of p-AKT, Nrf2 and HO-1 was significantly up-regulated(P<0.05 or P<0.01). CONCLUSION EMPA and DAPA have protective effects on PA-induced cardiomyocyte injury, and the mechanism may be related to down-regulation of TLR4 and p-mTOR protein expression, enhancement of AKT protein phosphorylation, activation of Nrf2/HO-1 pathway, and inhibition of ROS generation.
