【作者】 史玥；

【导师】 吴中海；

【作者基本信息】 中国人民解放军第一军医大学 ， 神经生理学， 2003， 硕士

【摘要】 目的 1)应用新生大鼠离体延髓脑片标本，同步记录舌下衬经根和面神经后核内侧区(the medial area of retro facialis nucleus，mNRF)的呼吸神经元单位的放电活动，观察不同浓度异丙酚(2，6-diisopropylphenol，propofol)对延髓基本呼吸中枢吸气神经元放电活动的作用规律。2)应用γ-氨基丁酸A受体(GABA_A受体)和甘氨酸(Glycine，Gly)受体相应的拮抗剂，观察异丙酚对吸气神经元放电活动的影响，进一步探讨异丙酚对延髓基本呼吸节律中枢吸气衬经元的可能机制。 方法 选用新生SD大鼠(0-3d)，雌雄不拘。参照并改良Suzue的方法制作离体延髓脑片标本，记录舌下神经放电作为呼吸活动的监测指标，并在延髓腹外侧区同步记录吸气神经元单位的放电活动。以改良的Kreb’s液(the modified Kreb’s solution，MKS)灌流离体延髓脑片，将实验随机分成Ⅰ～Ⅶ组(每组n=6)。Ⅰ组为空白对照组(MKS组)，第Ⅱ～Ⅴ组异丙酚浓度分别为5μmol/L、20μmol/L、50μmol/L、100μmol/L持续灌流3min，第Ⅵ组给GABA_A受体特异性阻断剂荷包牡丹碱(Bicuculline，20μmol/L)与异丙酚20μmol/L，第Ⅶ组给甘氨酸受体特异性拮抗剂士的宁(STR，100μmol/L)，观察给药后1、3、5、10、15、30min时吸气神经元放电时程和峰值、呼气时程(吸气神经元放电静止期)和呼吸频率的变化。 结果 1)Ⅰ组各项参数指标在各时间点均无显著性变化(P＞0.05)。2)第Ⅱ～Ⅴ组在1～30min内吸气神经元放电时程均表现为逐渐显著减小，15min时作用最显著，且各组与MKS灌流的空白对照组相比均有显著性差异。3)第Ⅱ～Ⅴ组1min内呼气时程无显著性变化，3～30min内呼气时程均表现为显著延长，5～15min内达到其最大效应。4)各组在1～3min内吸气神经元放电峰值增加，10～30min内放电峰值与给药前相著变化，但与1一3min时的放电峰值比显著降低，呈到乙先州加介_后阵低的趋势，各组间放电峰值无显著性差异。5)各组在3一3omil:内口于吸频率逐渐减慢，5一巧min内达到其最大抑制效应。各组l句呼吸频率的变化无显著性差异。6)荷包牡丹碱十异丙酚灌流组的吸气时程和呼气时程给子肠可后均无显著性差异。7)士的宁+异丙酚灌流组的吸气!!寸程给药前后无」，‘(著性差异，呼气时程在给药后IOmin、15mll7、 3Omi。时与给药前相比有显著性差异。 结论:以上结果提示: 1)异丙酚可抑制新生大鼠离体延髓脑片标本吸气神经元的放电时程，主要表现为使吸气神经元的放电静止期的时程明显延长，此抑制作用具有浓度依赖性。 2)异丙酚可以使呼吸频率随着给药时间的延民而降低，但此抑制作用对吸气神经元的放电峰值没有明显的抑制作用。 3)GABAA受体可能介导了异丙酚对延髓基本呼吸中枢吸左讨中经元放电活动}_lrJ抑制作用。 4)甘氨酸受体可能也参与了异丙酚对延髓华本r.『’、川}、}吸一、砷:、，几放电时程的抑制作用。更多还原

【Abstract】 Objective:1.To investigate the effects of propofol on the discharge of inspiratory neurons in the brainstem slices from neonatal rats2.To study the mechanism of propofol on the discharge of inspiratory neurons in the brainstem slices from neonatal rats. Methods:Experiments were performed on in vitro brainstem slices from neonatal rats. Newborn SD rats (0-3days) of either sex were used. Respiratory rhythmical discharge activity of the hypoglossal nerve was recorded by suction electrode. Extracellular recordings were made from 42 neuronal units with respiratory-related rhythmical activity. The effects of propofol on the inspiratory neurons were recorded by adding these drugs into the perfused modified Kreb’s solution (MKS). Forty two neuronal units were divided into 7 groups: group 1 : control group in which neuronal units were perfused with MKS only, group II ~ V: propofol groups in which neuronal units were perfused continuously for 3 min with different concentrations of propofol(5,20,50,100μmol/L). group VI: bicuculline-propofol group in which neuronal units were continuously perfused with a specific GABAA receptor blocker, bicuculline(Bic, 20nmol/L)and propofol(20umol/L). group VII: strychnine-propofol group in which neuronal units were continuously perfused with a specific Gly receptor blocker, strychnine(STR, 100μmol/L)and propofol(20μmol/L).The discharge time of inspiratory, expiratory, the peak value of inspiratory discharge and the frequency of respiration were recorded before and 1, 3, 5, 10, 15, 30min after propofol or bicuculline-propofol or strychnine-propofol perfusion. Results:1. In control group, there was no significant change in all parameters at the designated time internals.2. In group II ~IV, at Imin to 30min after propofol perfusion, the dischargetime significantly became shorter and at 5min, 4 out of 6 neuronal units were stopped in group V (propofol 100μmol/L). The inspiratory discharge time was inhibited in a concentration-dependent manner in 11 ~IV group. At 3min to 30min, the expiratory times become prolonged and frequency of respiration showed decrease.3. With the application of bicuculine(20μmol/L) and propofol(20μmol/L), the discharge time of inspiratory neurons and expiratory time did not change significantly after perfusion.4. With the application of strychnine(100μmol/L) and propofol(20μmol L). the discharge time of inspiratory neurons did not change significantly after perfusion and expiratory time still become prolonged significantly at 10min, 15min. 30min after perfusion.Conclusion:1. Propofol inhibits the discharge of inspiratory neurons in a concentration-dependent manner as shown by short of discharge time of inspiratory neurons and prolongation of the times of expiration.2. GABAA receptor may play an important ’role in inhibitory action of propofol on inspiratory neuron in the isolated brainstem slices from neonatal rats.3. Gly receptor may take part in the role in inhibitory action of propofol on the isolated brainstem slices from neonatal rats.更多还原