Effects Of Dexmedetomidine On Hippocampal Pyroptosis And Learning And Memory Impairment Induced By Propofol In The Developing Rats

Objective:In order to investigate that dexmedetomidine can improve learning and memory impairment induced by propofol in developing rats,and whether it is related to reducing inflammatory response and inhibiting pyroptosis by regulating NLRP3,Caspase-1,GSDMD and ASC proteins.Methods:On the seventh day take eighty newborn SD rats,according to random number table method is divided into four groups(n = 20): the control group(Con group)intraperitoneal injection capacity such as physiological saline,the propofol group(Pro group)intraperitoneal injection of propofol 100 mg/kg,the dexmedetomidine group(Dex group)intraperitoneal injection of 25 ug/kg,the dexmedetomidine pre-administration group(Dex+Pro group)intraperitoneal injection of dexmedetomidine 25 ug/kg,according to Pro group after 20 mins regimen.After waking up 2 hours,the head was severed and the hippocampal tissue was collected.The remaining 10 animals in each group were reared in the same litter until 30 days later.Take Morris water maze was used to detect spatial learning and memory ability of 30-day-old rats.Western Blot was used to measure the protein expression levels in hippocampal tissues of 7-day-old rats at 2 hours after anesthesia and immediately after Morris water maze at 35 days of age.The expression levels of IL-1βand IL-18 in hippocampal tissues were measured by Enzyme-linked Immunosorbent Assay(ELISA).Results:There was no significant difference in Sp O2 among the four groups(P > 0.05).After waking up 2 hours 7 days of age :(1)Western Blot :Compared with Con group,NLRP3,GSDMD,Caspase-1 and ASC proteins in hippocampus of Pro group were significantly increased(P<0.05),Compared with Dex+Pro group(P< 0.05),Compared with Pro group,the expression of various proteins in the hippocampus of Dex group and Dex+Pro group were significantly decreased(P<0.05).(2)ELISA:Compared with Con group,the concentrations of inflammatory factors IL-1β and IL-18 in hippocampus of Pro group were significantly increased(P<0.05),Compared with the concentration of IL-18 in Dex +Pro group(P<0.05).Compared with Pro group,the concentrations of inflammatory factors IL-1β and IL-18 in Dex group and Dex +Pro group were significantly decreased(P<0.05).35 Days of age :(1)Western Blot:Compared with Con group,the protein expressions of NLRP3,Caspase-1,GSDMD and ASC in Pro group were significantly increased(P<0.05).Compared group was significantly increased(P<0.05);Compared with Pro group,the release of inflammatory factors in Dex group and Dex+Pro group was significantly decreased with Pro group,the protein expressions of NLRP3,Caspase-1,GSDMD and ASC in Dex group and Dex +Pro group were significantly down-regulated(P<0.05).(2)ELISA:Compared with Con group,the concentrations of inflammatory factors IL-1βand IL-18 in hippocampus of Pro group were significantly increased(P<0.05),Compared with the concentration of IL-18 in Dex +Pro group(P<0.05).Compared with Pro group,the concentrations of inflammatory factors IL-1β and IL-18 in Dex group and Dex +Pro group were significantly decreased(P<0.05).(3)Animal behavior testing:The escape latency of the four groups of rats was not statistically significant on the first day.From day 2 to day 4,compared with Con group,the escape latency of Pro group was significantly prolonged(P<0.05).Compared with Pro group,the escape latency of Dex group and Dex +Pro group were significantly shorted(P<0.05).Compared with Con group,the total number of platform crossing in Pro group was significantly decreased(P<0.05).Compared with Pro group,the total times of platform crossing in Dex group and Dex+Pro group were significantly increased(P<0.05).Conclusion:Dexmedetomidine may alleviate the inflammatory response and pyroptosis induced by propofol in the hippocampus of developing rats by inhibiting the proteins expressions of NLRP3,ASC,Caspase-1 and GSDMD in the hippocampus and reducing the release of inflammatory factors,thus improving the learning and memory impairment of rats.