丙泊酚镇静对大鼠海马BDNF-TrkB/p75信号和认知功能的影响

Effects of propofol sedation on BDNF-TrkB/p75 signal and cognitive function in rat hippocampus

目的·探讨丙泊酚镇静对大鼠认知功能的影响及其可能的机制。方法·48只SD大鼠被随机分为3组。10 mg/m L丙泊酚注射液以100 mg/kg或300 mg/kg腹腔注射45 min后,用定量PCR检测大鼠海马脑源性神经营养因子(brain derived neurotropic factor,BDNF)-Trk B/p75信号分子的m RNA水平;并用逃避性抑制(inhibitory avoidance,IA)试验评价丙泊酚作用后的大鼠学习记忆情况。结果·丙泊酚腹腔注射45 min后,100 mg/kg组和300 mg/kg组大鼠海马组织中BDNF的m RNA水平分别是对照组的(1.20±0.13)倍(P=0.002)和(88±12)%(P=0.044);100 mg/kg组和300 mg/kg组大鼠海马组织中Trk B的m RNA水平分别是对照组的(1.01±0.11)倍(P=0.982)和(86±11)%(P=0.018)。另外,p75的m RNA水平分别是对照组的(1.02±0.10)倍(P=0.778)和(1.59±0.18)倍(P=0.000)。100 mg/kg组大鼠IA的潜伏期与对照组的差异无统计学意义(P=0.875);300 mg/kg组大鼠IA的潜伏期显著低于对照组(P=0.028),亦显著低于100 mg/kg组(P=0.020)。结论·丙泊酚呈剂量依赖性调节海马BDNF-Trk B/p75信号分子的表达,高剂量丙泊酚可能通过调节海马BDNF-TrkB/p75信号进而影响大鼠的认知功能。

Objective·To detect the effects of propofol sedation on cognitive function in rats and its mechanism.Methods·Forty-eight SD rats were randomly divided into three groups,i.e.control group,100 mg/kg group and 300 mg/kg group.Rats were administrated intraperitoneally with propofol(10 mg/mL,100 mg/kg or 300 mg/kg).The mRNA levels of brain derived neurotropic factor(BDNF)-TrkB/p75 signal molecules in rat hippocampus were evaluated by realtime PCR 45 min after propofol treatment.Learning and memory ability was examined by inhibitory avoidance(IA)test after propofol treatment.Results·The mRNA levels of BDNF in the hippocampal tissue were(1.20±0.13)fold(P=0.002)and(88±12)%(P=0.044)of that in control group,respectively,in 100 mg/kg group and 300 mg/kg group after injection of propofol.The mRNA levels of TrkB were(1.01±0.11)fold(P=0.982)and(86±11)%(P=0.018)of that in control group,respectively,in 100 mg/kg group and 300 mg/kg group.The mRNA levels of p75 were(1.02±0.10)fold(P=0.778)and(1.59±0.18)fold(P=0.000)of that in control group,respectively,in 100 mg/kg group and 300 mg/kg group.There was no significant difference of the 24 h IA memory retention latency between 100 mg/kg group and control group.The 24 h IA memory retention latency in 300 mg/kg group was significantly decreased compared with control group(P=0.028)and 100 mg/kg group(P=0.020).Conclusion·Propofol dose-dependently regulates the expression of BDNF-TrkB/p75 signal molecules,and high dose propofol may reduce cognitive function via BDNF-TrkB/p75 signal.