不同剂量5-羟色胺受体配体对慢性间歇低氧大鼠颏舌肌长时程易化的影响

摘要

目的 探讨不同剂量5-羟色胺2A/2C受体激动剂与5-羟色胺2A受体拮抗剂对慢性间歇低氧(CIH)大鼠颏舌肌放电活性长时程易化(LTF)的影响.方法 成年雄性SD大鼠30只,体重180～200g,通过随机数字表法将大鼠分为常氧对照组(A组,5只)和慢性间歇低氧组(CIH组,25只),其中CIH组分成5个亚组,分别为生理盐水组(B组)、5-羟色胺2A/2C受体激动剂30 μg组(C组)、5-羟色胺2A/2C受体激动剂50 μg组(D组)、5-羟色胺2A受体拮抗剂10 μg(E组)、5-羟色胺2A受体拮抗剂70 μg组(F组),每组各5只.CIH组大鼠放置于常压间隙低氧动物仓中,常氧组放置于常压常氧动物仓中,每天8h,连续处理4周,随后给予急性间歇低氧刺激,每次5 min,共3次,记录和比较各组大鼠给药前后颏舌肌肌电活性的变化.结果 B组大鼠颏舌肌放电活性明显高于A组.A组与B组在60 min时的放电幅度分别为(25.38±0.89)和(42.29±1.78)μV,差异有统计学意义(P＜0.01).与B组比较,C组和D组颏舌肌的放电幅度先上升后下降,上升幅度的差异具有统计学意义(P＜0.05).与B组比较,E组对颏舌肌的放电幅度影响不明显,差异无统计学意义(P＞0.05);但给予5-羟色胺2A受体拮抗剂70 μg后(F组),颏舌肌的放电幅度先下降后逐渐恢复至基础状态时的水平,下降幅度的差异具有统计学意义(P＜0.01).结论 CIH能够诱导颏舌肌LTF,5-羟色胺2A/2C受体激动剂可增强CIH大鼠颏舌肌放电活性,而5-羟色胺2A受体拮抗剂可降低CIH大鼠颏舌肌放电活性,二者均存在量效关系.%Objective To explore the effects of different doses of 5-HT2A/2CR agonist or 5-HT2AR antagonist on genioglossus discharge in chronic intermittent hypoxia rats.Methods Thirty adult male Sprague-Dawley rats,each 180-200 g,were randomly divided into the normoxia group (group A,n =5) and the chronic intermittent hypoxia group (CIH group,n =25) by the random number table.The rats in the CIH group were fed in the intermittent hypoxia animal chambers,while the normoxia control group was placed in the normoxia animal chambers for 8 h per day for 4 consecutive weeks.After 28 days,5 rin × 3 times of stimulation with acute intermittent hypoxia (AIH) were given and the genioglossus muscle activity were then recorded and compared before and after intravenous injection of saline (group B,n =5),the 5-HT2A/2CR agonist 30 μg/3 μl (group C,n =5) or 50 μg/5 μl group (group D,n =5),5-HT2AR antagonist 10 μg/1 μl (group E,n =5) or 70 μg/7 μl (group F,n =5).Results The average peak amplitude in 60 min of genioglossus muscle activity in the CIH saline control group (group B) was significantly higher than that in the normo0ia group (group A),while the genioglossus discharge in the 2 groups were (42.29 ± 1.78) μV,(25.38±0.89) μV respectively(P ＜0.01).The 5-HT2A/2C R agonist (30 0g/3 μl or 50 μg/5 0l) caused the amplitude of genioglossus muscle activity firstly to increase and then to decrease,with the peak changes showing statistical difference (P ＜ 0.05).10 μg/1 μl 5-HT2A R antagonist did not influence genioglossus muscle activity (P ＞ 0.05),however,after intravenous injection of 70 μg/7 0l 5-HT2A R antagonist,the amplitude of genioglossus discharge firstly decreased and then gradually returned to baseline level,the difference being statistically significant,P ＜ 0.01.Conclusion Our results indicate that CIH strengthens the genioglossus discharge in CIH rats.The 5-HT2A/2C R agonist can strengthen the genioglossus discharge but the 5-HT2A R antagonists can weaken the effect,both of which have dose-related effects.