Abstract：
BACKGROUND: Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia.
METHODS: Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia.
RESULTS: Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon.
CONCLUSIONS: The results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.
METHODS: Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia.
RESULTS: Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon.
CONCLUSIONS: The results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.
摘要：
背景：间歇性低氧以5-HT依赖性方式诱导通气反应增加。本研究旨在探讨中缝菌5-羟色胺1A受体（5-HT1A）受体对间歇性缺氧引起的通气反应增强的影响。
方法：对成年雄性大鼠进行立体定向手术，手术恢复后建立急性和慢性间歇性缺氧模型。实验组接受了将5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢化萘（8-OH-DPAT）显微注射到中缝大核（RMg）中。同时,对照组接受微量注射人工脑脊液代替8-OH-DPAT。比较了不同氧气状态组的通气反应。慢性间歇性缺氧后，通过免疫组织化学评估RMg区域的5-HT表达。
结果：与常氧组相比，急性间歇性缺氧组表现出更高的通气反应(例如，更短的吸气时间和更高的潮气量，呼吸频率,分钟通风,和平均吸气流量）（P<0.05）。8-OH-DPAT显微注射部分削弱了急性间歇性缺氧组的这些变化。Further,与急性间歇性低氧组相比，慢性间歇低氧组大鼠在1天的间歇低氧后通气反应指标较高(P<0.05)。这些作用在间歇低氧治疗3天后达到峰值，然后逐渐降低。此外，这些变化在实验组中减少。慢性间歇性缺氧后RMg区5-HT表达增加,这与通气反应的变化趋势一致。虽然RMg区域中5-HT1A受体的激活减轻了这种现象。
结论：结果表明RMg5-HT1A受体，通过改变5-HT在RMg区的表达水平，参与调节间歇性缺氧引起的通气反应增加。
方法：对成年雄性大鼠进行立体定向手术，手术恢复后建立急性和慢性间歇性缺氧模型。实验组接受了将5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢化萘（8-OH-DPAT）显微注射到中缝大核（RMg）中。同时,对照组接受微量注射人工脑脊液代替8-OH-DPAT。比较了不同氧气状态组的通气反应。慢性间歇性缺氧后，通过免疫组织化学评估RMg区域的5-HT表达。
结果：与常氧组相比，急性间歇性缺氧组表现出更高的通气反应(例如，更短的吸气时间和更高的潮气量，呼吸频率,分钟通风,和平均吸气流量）（P<0.05）。8-OH-DPAT显微注射部分削弱了急性间歇性缺氧组的这些变化。Further,与急性间歇性低氧组相比，慢性间歇低氧组大鼠在1天的间歇低氧后通气反应指标较高(P<0.05)。这些作用在间歇低氧治疗3天后达到峰值，然后逐渐降低。此外，这些变化在实验组中减少。慢性间歇性缺氧后RMg区5-HT表达增加,这与通气反应的变化趋势一致。虽然RMg区域中5-HT1A受体的激活减轻了这种现象。
结论：结果表明RMg5-HT1A受体，通过改变5-HT在RMg区的表达水平，参与调节间歇性缺氧引起的通气反应增加。
