Background
Sevoflurane, an inhalational general anesthetic, has become one of the most widely used inhalational anesthetics in surgery. However, previous studies have found that sevoflurane anesthesia can trigger an inflammatory response, resulting in secondary damage. Dexmedetomidine (DEX), a highly-selective α adrenergic receptor agonist, is widely used as an anesthetic adjuvant in the clinic. In this study we investigated whether DEX was able to suppress sevoflurane-induced neuroinflammation.
Conclusions
These data suggest that the PI3K/Akt/mTOR pathway contributes to sevoflurane-induced neuroinflammation and that activation of PI3K/Akt/mTOR signaling by DEX could help reduce the neuroinflammatory effects of sevoflurane.
Methods
The aim was to determine the mechanism of action of the suppressive effect of DEX using a rat model. Rats were randomly divided into a control group (n = 10), low-dose sevoflurane group (L-Sev; n = 10), high-dose sevoflurane group (H-Sev; n = 10), vehicle group (n = 10), DEX group (n = 10) and DEX + LY294002 (a specific inhibitor of PI3K) group (n = 10). The rats in vehicle, DEX and DEX + LY294002 groups were in the presence of high-dose sevoflurane exposure. Western blotting was used to measure the expression of proinflammatory cytokines (IL-6, IL-8, TNF-α) and the activity level of the phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway.
Results
We found that sevoflurane anesthesia induced an increase in the levels of pro-inflammatory cytokines, while decreasing activation of the PI3K/Akt/mTOR pathway in both the cortex and hippocampus of rats. Treatment with DEX reduced pro-inflammatory cytokine levels and prevented inactivation of the PI3K/Akt/mTOR pathway. Moreover, LY294002, an inhibitor of the PI3K/Akt/mTOR pathway, reduced the anti-inflammatory activity of DEX. Conclusions: These data suggest that the PI3K/Akt/mTOR pathway contributes to sevoflurane-induced neuroinflammation and that activation of PI3K/Akt/mTOR signaling by DEX could help reduce the neuroinflammatory effects of sevoflurane.