Abstract
Myocardial cells in patients with diabetes mellitus (DM) experience more severe reperfusion injury following heart ischemia compared with those in patients without DM. The inflammatory response plays a key role in the process of myocardial ischemia-reperfusion (I/R) injury in diabetic patients. Dexmedetomidine (DEX) exhibits anti-inflammatory properties, indicating it is an effective treatment for diabetic myocardial I/R injury. C57BL/6 mice underwent 30 min of myocardial ischemia followed by 2 h of reperfusion. H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. DEX was administered at the onset of myocardial reperfusion in the mice or during reoxygenation of the H9c2 cells. Additionally, in an in vitro experiment, the Toll like receptor (TLR) 2 agonist Pam3CSK4 (PAM) was co-administered with DEX. Analysis of in vivo data demonstrated that DEX reduced serum inflammatory factor levels, myocardial infarction area and structural tissue damage following myocardial I/R in diabetic mice. Immunohistochemical staining and western blot analysis revealed that DEX decreased TLR2 expression after myocardial I/R in these mice. Western blot analysis also demonstrated that DEX reduced the expression of NF-κB and TNF-α. Analysis of in vitro data indicated that DEX increased the viability of H9c2 cells after OGD/R under high-glucose conditions. DEX achieved this by inhibiting NF-κB activation through downregulation of TLR2 expression, thereby reducing the inflammatory response. However, the effects of DEX in H9c2 cells were reversed by the application of the TLR2 agonist PAM. DEX may have protected the hearts of diabetic mice from I/R injury by reducing inflammation through the downregulation of the TLR2 signaling pathway.