Remimazolam Combined with Andrographolide Improve Postoperative Cognitive Dysfunction in Rats after Cardiopulmonary Bypass through the AMPK/SIRT1 Signaling Pathway.

Abstract

Introduction: The effects of remimazolam (Re) in combination with andrographolide (AP) on learning, memory, and motor abilities in rats following cardiopulmonary bypass (CPB) surgery were studied.

Methods: We hypothesized that the combination of Re and AP could improve postoperative cognitive dysfunction (POCD) in rats after CPB by modulating nervous system inflammation. Cognitive function was assessed using the Morris Water Maze test, and the concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis was evaluated using western blotting and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay.

Results: The results indicated that both Re and AP independently improved cognitive function in rats after CPB and inhibited the secretion of inflammatory factors and apoptosis in hippocampal tissues. Combined administration of Re and AP enhanced the alleviation of POCD compared with monotherapy. The adenosine monophosphate-activated protein kinase/silent information regulator of transcription 1 (AMPK/SIRT1) signaling pathway was activated by the combination of Re and AP.

Conclusions: Collectively, the combination of Re and AP treatment significantly improves POCD in rats after CPB through activation of the AMPK/SIRT1 signaling pathway.