P300 Inhibition Improves Cell Apoptosis and Cognition Impairment Induced by Sevoflurane Through Regulating IL-17A Activation.

Abstract

Sevoflurane (Sev) is a rapidly acting, potent inhalation anesthetic with rapid uptake and elimination. But many studies have shown that Sev could result in cognition dysfunction in adolescent or aging patients. Now, therapeutic targeting with IL-17A antibody has shown a promising effect on Sev-induced cognition impairment. In the study we report that P300 inhibition could act as an alternative approach to decrease IL-17A activity. SHSY5Y cells were treated with Sev and cell apoptosis was evaluated by Annexin V-FITC/PI staining. The expression of P300 and IL-17A were assessed by Western blotting. Water maze tests were conducted in order to assess the cognitive function. We found that P300 and IL-17A were activated in SHSY5Y cells treated with Sev. P300 inhibitor C646 could reduce the apoptosis induced by Sev through decreasing IL-17A avtivity. Furthermore, IL-17A expression was upregulated after neurons were transfected with P300 expression plasmid and IL-17A expression was downregulated after neurons were incubated with P300 inhibitor C646. P300 overexpression could upregulate the promoter activity of IL-17A. Finally, in a rat model treated with Sev, we also found C646 to significantly improve the cognition impairment through the IL-17A pathway. These data show that P300 will potentially be a new drug target for the therapy of cognition impairment caused by Sev.