Open AccessDexmedetomidine protects cardiomyocytes against hypoxia/reoxygenation injury via multiple mechanisms
Author(s) -
Cai Shunv,
Liu Yixing,
Cheng Yun,
Yuan Junbo,
Fang Jun
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24119
Subject(s) - propidium iodide , viability assay , chemistry , apoptosis , superoxide dismutase , oxidative stress , lactate dehydrogenase , pharmacology , reactive oxygen species , dichlorofluorescein , reperfusion injury , malondialdehyde , microbiology and biotechnology , programmed cell death , biochemistry , ischemia , medicine , biology , enzyme
Abstract Background Myocardial infarction (MI) is a serious cardiovascular disease associated with myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine (Dex), an α2‐adrenoceptor agonist, has been reported to protect against I/R injury. We examined the cardioprotective effects of Dex on cardiomyocytes under hypoxia/reoxygenation (H/R) conditions and explored the underlying mechanisms. Materials and methods A H/R model was established to mimic the MI injury. The CCK‐8 assay was performed to measure cell viability. Cellular apoptosis was measured using the Annexin V fluorescein isothiocyanate (FITC)‐propidium iodide (PI) staining. The levels of interleukin (IL)‐1α and tumor necrosis factor (TNF)‐α, and the activity of lactate dehydrogenase (LDH) were measured using a commercial enzyme‐linked immunosorbent assay (ELISA) kit. Reactive oxygen species (ROS) were measured using the 2'‐7’ dichlorofluorescein diacetate (DCFH‐DA) staining assay. In addition, the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), catalase (CAT), and caspase‐3 were measured using a commercial kit. siRNA was used to silence Bcl‐2, catalase, or STAT3. Western blotting was used to measure the change in the levels of proteins. Results Dex improved the cell viability and inhibited the inflammatory response in H9c2 cells exposed to H/R treatment. In addition, Dex inhibited apoptosis and alleviated the endoplasmic reticulum (ER) stress and oxidative stress in H9c2 cells under the H/R treatment. Mechanism investigation showed that Dex inhibited the intrinsic pathway of apoptosis. Moreover, Dex enhanced the activation of the JAK2/STAT3 signaling pathway in H/R‐treated H9c2 cells. Conclusion Altogether, our findings suggested Dex as a promising therapeutic agent for myocardial I/R.