MCC950 improves perioperative cognitive disorders in rats undergoing cardiopulmonary bypass through inhibiting the NOD like receptor thermal protein domain associated protein 3/caspase-1 pathway
Objective To investigate the protective effect of MCC950,the NOD like receptor thermal protein domain associat-ed protein 3(NLRP3)inflammasome inhibitor on perioperative neurocognitive disorders(PND)in rats undergoing cardiopulmonary by-pass(CPB).Methods According to the random number table method,30 clean adult male SD rats,weighing 350-450 g,were divid-ed 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 nor-mal 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/cas-pase-1 pathway to improve PND in CPB rats.
NOD like receptor thermal protein domain associated protein 3CaspasePerioperative neurocognitive disor-dersCardiopulmonary bypassMCC950
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