Dexmedetomidine protects cardiomyocytes against hypoxia/reoxygenation injury via multiple mechanisms

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.

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.

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.

Altogether, our findings suggested Dex as a promising therapeutic agent for myocardial I/R.