Effect of clemastine fumarate on TLR4/PI3K/Akt signaling pathway during hypoxia-reoxygenation in rat cardiomyocytes
10.3760/cma.j.issn.0254-1416.2019.05.026
- VernacularTitle:富马酸氯马斯汀对大鼠心肌细胞缺氧复氧时TLR4/PI3K/Akt信号通路的影响
- Author:
Ru YAN
1
;
Feng YUE
;
Yongxin LIU
;
Xiaoxiao YUAN
;
Meiyan SUN
;
Rui ZHANG
;
Zhaodong JUAN
;
Yaru HUANG
;
Jizhe SHEN
Author Information
1. 潍坊医学院麻醉学系 山东省医药卫生临床麻醉重点实验室 261053
- Keywords:
Histamine H1 antagonists;
Myocardial reperfusion injury;
Toll-like receptor 4;
Phosphatidylinositol 3-kinases;
Protein-serine-threonine kinases
- From:
Chinese Journal of Anesthesiology
2019;39(5):610-612
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of clemastine fumarate on Toll-like receptor 4/phosphatidylinositol-3-kinase/serine-threonine kinase (TLR4/PI3K/Akt) signaling pathway during hypoxia-reoxygenation (H/R) in rat cardiomyocytes.Methods H9C2 cells of rats cultured in vitro were seeded in culture wells or dishes at a density of 1×105 cells/ml and divided into 3 groups (n=11 each) by using a random number table method:control group (group C),H/R group and clemastine fumarate group (CF group).Cardiomyocytes were exposed to 5％ CO2-95％ N2in a low-glucose DMEM medium at 37℃ for 4 h followed by 4 h reoxygenation.At 4 h of reoxygenation,the cell viability was detected by CCK-8 assay,the ultrastructure was observed with a transmission electron microscope,the expression of TLR4,PI3K,phosphorylated Akt (p-Akt) and caspase-3 was detected by Western blot,and the expression of TLR4,PI3K and caspase-3 was detected by immunofluorescence.Results Compared with group C,the cell viability was significantly decreased,the expression of TLR4 and caspase-3 was up-regulated,and the expression of PI3K and p-Akt was down-regulated in group H/R (P＜0.05).Compared with group H/R,the cell viability was significantly increased,the expression of TLR4 and caspase-3 was down-regulated,the expression of PI3K and p-Akt was up-regulated (P＜0.05),and the mitochondrial damage was significantly attenuated in group CF.Conclusion The mechanism by which clemastine fumarate alleviates H/R injury to rat cardiomyocytes may be related to inhibiting TLR4 expression and activating PI3K/Akt signaling pathway.
