右美托咪定减轻丙泊酚诱导的发育期大鼠学习记忆障碍

Dexmedetomidne alleviates the learning and memory impairment induced by propofol in developing rats

中文关键词: 右美托咪定  神经保护  细胞焦亡

英文关键词: Dexmedetomidine  Neuropotection  Pyroptosis

中文摘要:

      
目的 探讨右美托咪定预给药对丙泊酚诱导的发育期大鼠学习记忆功能的影响，以及可能参与的炎症机制。
方法 健康新生SD大鼠48只，7日龄，体重12～20 g。采用随机数字表法分为四组：对照组（C组）、丙泊酚组（P组）、右美托咪定组（D组）和右美托咪定预给药组（DP组），每组12只。C组腹腔注射生理盐水0.1 ml；P组腹腔注射丙泊酚100 mg/kg；D组腹腔注射右美托咪定25 μg/kg，DP组先腹腔注射右美托咪定25 μg/kg，20 min后腹腔注射丙泊酚100 mg/kg。麻醉苏醒后将大鼠同窝饲养至30日龄，采用Morris水迷宫检测空间学习记忆能力。于大鼠水迷宫实验结束后断头取海马组织，采用Western blot法测量海马组织NOD样受体蛋白-3(NLRP3)、凋亡相关斑点样蛋白（ASC）、半胱氨酸天冬氨酸蛋白酶-1(caspase-1)、gasdermin-D 蛋白（GSDMD）蛋白含量，ELISA法测量海马组织白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）浓度。
结果 与C组比较，P组第2~4天逃避潜伏期明显延长，穿越平台次数明显减少（P<0.05）。与P组比较，D组和DP组第2~4天逃避潜伏期明显缩短，穿越平台总次数明显增多（P<0.05）。与C组比较，P组海马组织NLRP3、ASC、caspase-1和GSDMD蛋白含量明显升高（P<0.05）。与P组比较，D组和DP组海马组织NLRP3、ASC、caspase-1、GSDMD蛋白含量明显降低（P<0.05）。C组和D组海马组织NLRP3、ASC、caspase-1和GSDMD蛋白含量差异无统计学意义。与C组比较，P组海马组织IL-1β、IL-18浓度明显升高（P<0.05）。与P组比较，D组和DP组海马组织IL-1β和IL-18浓度明显降低（P<0.05）。
结论 右美托咪定预给药抑制海马组织细胞焦亡，改善丙泊酚诱导的发育期大鼠学习记忆障碍，可能与抑制了NLRP3、ASC、caspase-1、GSDMD蛋白上调以及炎性因子IL-1β、IL-18的释放有关。

英文摘要:

      
Objective To investigate the effect of dexmedetomidine pre-administration on learning and memory impairment induced by propofol in developing rats, as well as the inflammatory mechanisms that may be involved.
Methods Healthy SD rats aged 17 days, weighing 12-20 g, were randomly divided into 4 groups (n = 12): control group (group C), propofol group (group P), dexmedetomidine group (group D), and dexmedetomidine + propofol group (group DP). Group C was intraperitoneally injected with physiological saline 0.1 ml; group P was intraperitoneally injected with propofol 100 mg/kg, group D was intraperitoneally injected with dexmedetomidine 25 μg/kg; group DP was intraperitoneally injected with dexmedetomidine 25 μg/kg at first, then propofol 100 mg/kg 20 minutes later. After awakening from anesthesia, all the rats were reared together until 30 days of age. Morris water maze was used to test spatial learning and memory. Rat hippocampus was decapitated after the water maze experiment. Western blot was used to measure the protein expression levels [NOD-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin-D (GSDMD)] in the hippocampal tissues, and the expression levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by ELISA.
Results Compared with group C, the escape incubation period in group P was significantly prolonged from day 2 to day 4, and the number of crossing platform was significantly decreased (P < 0.05). Compared with group P, the escape incubation period in groups D and DP was significantly shortened from day 2 to day 4, and the total number of crossing platform was significantly increased in groups D and DP (P < 0.05). Compared with group C, the protein contents of NLRP3, ASC, caspase-1, and GSDMD of the hippocampusin in group P were significantly increased (P < 0.05). Compared with group P, the protein contents of NLRP3, ASC, caspase-1, and GSDMD of the hippocampus in groups D and DP were significantly decreased (P < 0.05). There were no significant differences in NLRP3, ASC, caspase-1, and GSDMD protein contents between group C and group D. Compared with group C, the concentrations of IL-1β and IL-18 in the hippocampus in group P were significantly increased (P < 0.05). Compared with group P, the concentrations of IL-1β and IL-18 in the hippocampus were significantly decreased in groups D and DP (P < 0.05).
Conclusion Dexmedetomidine pre-administration inhibited scortosis of hippocampal tissue and improved learning and memory impairment induced by propofol in developing rats, which may be related to inhibition of up-regulation of NLRP3, ASC, caspase-1, and GSDMD proteins and release of inflammatory factors IL-1β and IL-18.