Previous studies have indicated that gut-derived
endotoxin played a pivotal role for aggravating systemic inflammatory response to multi-organ dysfunction under
heatstroke.
Dexmedetomidine (DEX) could protect against
inflammation and multi-organ injury in various scenarios. The aim of this study was to explore the protective effect of DEX on
heatstroke and the mechanism involved. Male C57BL/6 mice were placed in a controlled climate chamber (40 ± 1°C) until the maximum core temperature (Tc, Max) of 42.7°C, the received criterion of
heatstroke, was attained, DEX (25 μg/kg) or
0.9% saline was injected intraperitoneally immediately. The results showed that DEX could significantly attenuate multi-organ injury induced by
heatstroke, simultaneously decrease levels of serum inflammatory
cytokines through inhibiting the intestinal nuclear factor-κB activation. Furthermore, to assess the effects of DEX on intestine mucosal barrier under
heatstroke, the levels of plasma
endotoxin, FD4, and D-
lactate were detected and the expression of
tight junction proteins occludin and ZO-1 was analyzed by western blot and immunohistochemistry. Meanwhile, transmission electron microscopy was employed to confirm the ultrastructure of intestine. Interestingly, we found that DEX decreased the intestinal permeability and sustained the integrity of intestinal barrier. Finally, to evaluate the anti-apoptosis effect of DEX, the
pro-apoptotic protein Bax and
anti-apoptotic protein Bcl-2 were analyzed by western blot, and
terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted. The results showed that DEX decreased TUNEL-positive cells induced by
heatstroke in a Bax/Bcl-2-related manner. Taken together, our results indicate that DEX could protect against
inflammation and multi-organ injury induced by
heatstroke via sustaining the intestinal integrity.