摘要目的 探讨5-羟色胺2A受体(5-HT2AR)和蛋白激酶C(PKC)通路在慢性间歇低氧(CIH)大鼠颈动脉体窦神经(CSN)放电活性长时程易化(LTF)中的调节作用.方法 采用数字表法将24只成年SD大鼠随机分为A组(生理盐水对照组)、B组(5-HT2AR拮抗剂组)、C组(PKC抑制剂组)和D组(5-HT2AR拮抗剂+PKC抑制剂组),每组6只.将动物置于低氧动物仓中进行间歇低氧处理,每天8h(9:00至17:00),连续4周.在稳定记录CSN电信号后,对A、B、C三组大鼠分别静脉给予生理盐水、5-HT2AR拮抗剂(ketanserin)或PKC抑制剂(PKC θ伪底物),10 min后再进行3次急性间歇低氧(AIH)处理,每次5 min,间隔5 min,之后立即记录CSN电信号.对D组大鼠,先给予ketanserin,10 min后给予PKC θ伪底物,再进行3次AIH刺激和CSN电信号记录.结果 四组大鼠在AIH处理前的基线CSN放电振幅差异无统计学意义(P＞0.05).经AIH处理后,A组大鼠在30min时CSN放电振幅为(5.01±0.53)μV,60 min时为(4.95±0.34) μV,明显高于AIH前水平(P＜0.01),提示AIH能够诱导CIH预处理大鼠发生CSN放电活性LTF.B组大鼠在注射ketanserin 后,AIH刺激30 min后CSN的放电振幅为(3.79±0.42)μV,60 min后为(3.73±0.46)μV,仍明显高于AIH前水平(P＜0.01),提示阻滞5-HT2AR并不能完全抑制大鼠窦神经LTF的产生.C组及D组大鼠在AIH刺激前后CSN的放电振幅均变化不明显,差异无统计学意义(P＞0.05),提示通过阻断PKC通路或5-HT2A R/PKC通路均可完全抑制CSN的LTF.结论 5-HT2AR及PKC通路参与调节了CIH大鼠发生的颈动脉体窦神经LTF.

abstractsObjective To explore the role of 5-HT2A R/PKC pathway in mediating long-term facilitation (LTF) of carotid sinus nerve (CSN) discharge in chronic intermittent hypoxia (CIH) rats.Methods With number table,24 adult SD rats were randomly divided into saline control group (group A,n =6),5-HT2AR antagonist (ketanserin) group (group B,n =6),PKC inhibitor (PKC θ-pseudosubstrate)group (group C,n =6) and combined ketanserin with PKC θ-pseudosubstrate group (group D,n =6).All rats were placed into the animal chambers for CIH treatment,8 h per day (from 9:00 to 17:00) for 4 consecutive weeks.28 days later,5 min × 3 times of stimulation with acute intermittent bypoxia (AIH)were given,after that,stable CSN discharge activities were recorded and compared before and after intravenous injection of saline (group A),ketanserin (group B),PKC θ-pseudosubstrate (group C) or ketanserin + PKC θ-pseudosubstrate (group D),respectively.Results There were no significant difference in the baseline (before AIH stimulation) average peak amplitude of CSN discharge among the four groups (P ＞ 0.05).In group A,the amplitude of CSN discharge at 30 min and 60 min after AIH were (5.01 ± 0.53) μV and (4.95 ± 0.34) μV respectively,which were significantly higher than that before AIH (P ＜0.01).The results implied that the CSN LTF could be induced by AIH in CIH pre-treatment rats.In group B,the amplitude of CSN discharge at 30 min and 60 min after AIH were (3.79 ± 0.42) μV and (3.73 ± 0.46) μV,respectively,which were still significantly higher than that before AIH (P ＜0.01),showing that carotid sinus nerve LTF couldn't be completely blocked by 5-HT2AR antagonist in rats.After injection of PKC θ-pseudosubstrate or ketanserin + PKC θ-pseudosubstrate in group C or D,there were no significant differences in CSN discharge amplitude before and after AIH (P ＞0.01),suggesting that inhibition of PKC alone or 5-HT2AR/PKC pathway could completely block the LTF of CSN.Conclusion 5-HT2AR/PKCpathway was involved in mediating long-term facilitation of carotid sinus nerve discharge in CIH rats.