Objective: To explore the role of 5-HT(2A)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-HT(2A)R 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 hypoxia (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-HT(2A)R 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-HT(2A)R/PKC pathway could completely block the LTF of CSN. Conclusion: 5-HT(2A)R/PKC pathway was involved in mediating long-term facilitation of carotid sinus nerve discharge in CIH rats.
目的： 探讨5－羟色胺2A受体(5－HT(2A)R)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－HT(2A)R拮抗剂组)、C组(PKC抑制剂组)和D组(5－HT(2A)R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8 h(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－HT(2A)R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30 min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－HT(2A)R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－HT(2A)R/PKC通路均可完全抑制CSN的LTF。 结论： 5－HT(2A)R及PKC通路参与调节了CIH大鼠发生的颈动脉体窦神经LTF。.
Keywords: 5-HT(2A)R; Carotid sinus nerve; Chronic intermittent hypoxia; Long-term facilitation; Protein kinase C.