β内啡肽对慢性缺氧大鼠呼吸的影响

目的　探讨β内啡肽（βＥＰ） 在慢性缺氧大鼠呼吸调控中的作用。方法　采用放射免疫法测定慢性缺氧大鼠模型血浆及延髓、桥脑、下丘脑、中央灰质等神经核团中βＥＰ的含量变化，以及不同给药途径给予外源性βＥＰ对慢性缺氧大鼠呼吸功能的影响。正常大鼠侧脑室注射βＥＰ后，观察记录呼吸频率（ＲＲ） ；１０２ 只慢性缺氧大鼠随机分为：（１） 静脉组３６ 只，分别给予阿片受体拮抗剂纳洛酮（ＮＬＸ） 和不同剂量βＥＰ，记录ＲＲ 和潮气量（ＶＴ）；（２） 侧脑室组４８ 只，微量注射ＮＬＸ、βＥＰ，测定ＲＲ、ＶＴ及血气指标；（３） 孤束核组１８ 只，分别注射βＥＰ和人工脑脊液（ＡＣＳＦ） ，测定ＲＲ和ＶＴ。结果慢性缺氧模型延髓、桥脑、下丘脑、中央灰质和血浆βＥＰ的含量较对照组均显著升高（Ｐ＜０－０１）。给正常大鼠侧脑室注射βＥＰ后，ＲＲ 显著下降（ Ｐ＜ ０－０５） 。慢性缺氧大鼠静脉给予不同剂量βＥＰ和ＮＬＸ后，ＲＲ和ＶＴ 变化差异无显著性（Ｐ＞０－０５）。侧脑室注射ＮＬＸ后，ＲＲ显著增高（ Ｐ＜０－０５）。侧脑室及孤束核注射βＥＰ后显著降低ＲＲ、ＶＴ。侧脑室注射ＮＬＸ３０ 分钟时ＭＶ／ＰａＣＯ２ 较对照组显著升高（ｔ＝２－７６ ，

Respiratory effects of beta endorphin in chronic hypoxic rats

OBJECTIVE: To assess the role of beta-EP in the physiological and pathophysiological process of respiratory regulation in chronic hypoxic rats. METHODS: The chronic hypoxic rat model was established by intravenous injections of papain 6 times, once a week. The concentration of beta-endorphin in medulla, pons, hypothalamus, central gray and plasma of chronic hypoxic rats were measured by radioimmunoassay. All animals were pretreated with sodium pentobartital (35 mg/kg) before experiment. 102 rats were randomly divided into three groups. Group 1 (n = 36). The respiratory rate (RR) and tidal volume (VT) were measured after intravenous injection of naloxone (NLX, 2 mg/kg), beta-EP (40 micrograms/kg, 160 micrograms/kg) or normal saline, Group 2 (n = 48). By the intracerebroventricular administration of NLX and beta-EP to the models, RR, VT and PaCO2 were observed after microinjection 5, 15, 30, 45, 60 min. Group 3 (n = 18). The respiratory effects of beta-EP after directly into the nucleus tractus solitari of the anaesthetised rats were investigated. RESULTS: The beta-EP contents in medulla, pons, hypothalamus, central gray and plasma of chronic hypoxic rats were significantly increased compared with control subjects (P < 0.01). It suggested that the pathophysiology of chronic hypoxic process infleuced the contents of beta-EP in the CNS and plasma in rats. Intracerebroventricular microinjection of beta-EP in normal rats, resulted in a significant decrease in RR (P < 0.05). No significant difference in RR and VT was observved after intravenous injection of naloxone (2 mg/kg) and beta-EP (40 micrograms/kg, 160 micrograms/kg) in treatment group compared with the control group (P > 0.05), Intracerebroventricular microinjection of NLX in chronic hypoxic rats, resulted in a marked increase in RR (P < 0.05) and central hypercapnic-sensitivity (t = 2.76, P < 0.05), Intracerebroventriculalr microinjection of beta-EP in chronic hypoxic models, resulted in severe respiratory depression after injection 15, 30, 45, 60 min (RR t = 3.41, 6.54, 6.97, 7.87, P < 0.01; VT t = 3.07, 7.27, 6.14, 6.08). CONCLUSIONS: These results indicate the beta-endorphin may be involved in central respiratory control of chronic hypoxic rats.