Abstract: Objective To investigate the protective effect of MCC950, the NOD like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome inhibitor on perioperative neurocognitive disorders (PND) in rats undergoing cardiopulmonary bypass (CPB). Methods According to the random number table method, 30 clean adult male SD rats, weighing 350‒450 g, were divided into three groups (n=10): a sham operation group (group S), a CPB group (group C) and a CPB+MCC950 (group CM). Rats in group S were not subject to CPB, while CPB was modeled in group C and group CM. Furthermore, group CM was injected with MCC950 at 10 mg/kg 24 h before CPB, 1 h before CPB, and 24 h after CPB, while group S and group C were injected with the equal volume of normal saline. Then, the water maze test was carried out 3 days after the operation to record the escape latency and the number of crossing the platform. Subsequently, the rats were sacrificed, and the hippocampal tissues were collected. Interleukin (IL)‑18 and IL‑1β contents were detected by enzyme‑linked immunosorbent assay, and caspase‑1 activity was detected by spectrophotometry. The protein levels of NLRP3, apoptosis‑associated speck‑like protein (ASC), pro‑caspase‑1 and gasdermin D (GSDMD) were detected by Western blot. The mRNA levels of NLRP3, ASC, and caspase‑1 were detected by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR). Results Compared with group S, group C and group CM showed prolonged escape latency (all P<0.05), with a reduced number of crossing the platform (all P<0.05), as well as increased contents of IL‑18 and IL‑1β and enhanced activity of caspase‑1 in hippocampal tissues (all P<0.05), up‑regulated protein levels of NLRP3, ASC, pro‑caspase‑1, and GSDMD (all P<0.05), and up-regulated mRNA levels of NLRP3, ASC, and caspase‑1 (all P<0.05). Compared with group C, group CM presented shortened escape latency (all P<0.05), with an increased number of crossing the platform (P<0.05), as well as decreased contents of IL‑1β and IL‑18 and weakened activity of caspase‑1 in hippocampal tissues (all P<0.05), down-regulated protein levels of NLRP3, ASC, pro‑caspase‑1 and GSDMD (all P<0.05), and down-regulated mRNA levels of NLRP3, ASC, and caspase‑1 (all P<0.05). Conclusion MCC950 can inhibit the NLRP3/caspase‑1 pathway to improve PND in CPB rats.
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