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Effect of clemastine fumarate on TLR4/PI3K/Akt signaling pathway during hypoxia-reoxygenation in rat cardiomyocytes

作者:Ru Yan, Feng Yue, Yongxin Liu, Xiaoxiao Yuan, Meiyan Sun, Rui Zhang, Zhaodong Juan, Yaru Huang · 发表于:Zhonghua mazuixue zazhi · 年份:2019 · DOI:10.3760/cma.j.issn.0254-1416.2019.05.026 · 被引用次数:1 · 研究领域:Immune Response and Inflammation、Traditional Chinese Medicine Analysis、Inflammatory mediators and NSAID effects

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% N2 in 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...