Obuchowicz Rafał, Sendur Ryszard, Pawlik Michał, Biernat Jarosław, Koprowska Bernadetta, Jaworek Jolanta, Thor Piotr J
Katedra Fizjologii Wydziału Lekarskiego Collegium Medicum Uniwersytetu Jagiellońskiego ul. Grzegórzecka 16, 31-531 Kraków.
Folia Med Cracov. 2002;43(1-2):95-109.
Adrenergic innervation plays an important role in the control of electric activity and circulatory parameters of the gut. Importance of adrenergic system as a modulator of motor, neural and metabolic activity of the intestine is studied extensively but still not well understood. We use 6-OHDA a neurotoxin and a blocking agent of adrenergic fibers, to evaluate their exact role in the control of vital parameters of the intestine and vagal nerves. 50 Wistar rats were used. Animals were fasted 24 h prior to experiment with free access to water allowed. Acute experiments were performed on 30 rats, divided in the three groups. Four experimental groups were established. I--sham operated. II and III--pretreated with 6-ODHA (25 mg//kg/24 h s.c.) 3 days before experiment. IV group were used for chronic procedure. Thiopental anesthesia (Vetbutal Biovet) was applied. Animals were artificially ventilated with positive pressure rodent ventilator (Ugo Basile), and heated with continuous temperature control by rectal thermistor (FST). Left carotid artery was cannulated and connected with electro manometer--arterial pressure (AP) was expressed in mm Hg. Right jugular vein was cannulated for continuous saline administration 0.2 ml/h. Mesenteric blood flow (MBF) was recorded with use of ultrasonic probe (Transonic systems T206). Microcirculatory blood Flow (LDBF) was estimated by laser Doppler flowmetry (Periflux 2001 Master). Arterio-venous difference (AVO2) was estimated from whole blood (AVOXimeter 1000 E). Oxygen uptake was calculated from MBF and AVO2 and expressed in ml/min/100 g tissue. Chronic experiments were performed on conscious animals with electrodes implanted to the serosal surface of the intestinal wall. Measurements of intestinal myoelectric parameters were performed one, two and three weeks after 6-OHDA administration. Vagal activity was recorded in left vagus nerve in the neck with suction electrodes (one month after 6-OHDA). 6-OHDA pretreatment evoked increase of dominant slow wave frequency by 0.1 Hz from 0.62 +/- 0.10 to 0.74 (+/- 0.03) Hz in the first week after treatment (p < 0.05). Slow wave frequency was no markedly influenced in acute experiments. In the chronic experiments after initial increase gradual decrease of slow wave frequency was observed reaching control values of 0.62 +/- 0.17 Hz after 28 days. After 6-OHDA administration in chronic experiments no substantial changes in slow waves amplitude was observed. Frequency and amplitude of spikes activity in vagus nerve after sympatectomy increased from 7.96 +/- 1.3 to 10.3 +/- 2/min and 0.18 +/- 0.09 to 1.13 +/- 0.8/mV. Chemical denervation evoked increase of MBF and LDBF by 18 +/- 3.6% and 22 +/- 6.4% respectively. Intestinal oxygen uptake (VO2) was increased by 10.2 +/- 1.2% in comparison to control. Heart rate and arterial pressure was decreased by 18 +/- 4% and 12 +/- 2.4% respectively in comparison to control. Adrenergic system plays profound role in the modulation of both myoelectric and motor activity of the intestine in the rat. Continuous activity of adrenergic neurons affects vascular conductance, capillary density and oxygen diffusion parameters.
肾上腺素能神经支配在控制肠道电活动和循环参数方面发挥着重要作用。作为肠道运动、神经和代谢活动调节因子的肾上腺素能系统的重要性已得到广泛研究,但仍未被充分理解。我们使用6-羟基多巴胺(6-OHDA),一种神经毒素和肾上腺素能纤维阻断剂,来评估它们在控制肠道和迷走神经重要参数方面的确切作用。使用了50只Wistar大鼠。实验前动物禁食24小时,允许自由饮水。对30只大鼠进行急性实验,分为三组。设立了四个实验组。I组——假手术组。II组和III组——在实验前3天用6-ODHA(25毫克/千克/24小时,皮下注射)预处理。IV组用于慢性实验。采用硫喷妥钠麻醉(Vetbutal Biovet)。动物用正压啮齿动物呼吸机(Ugo Basile)进行人工通气,并通过直肠热敏电阻(FST)进行连续体温控制加热。将左颈动脉插管并连接到电子压力计——动脉压(AP)以毫米汞柱表示。右颈静脉插管用于以0.2毫升/小时的速度连续输注生理盐水。使用超声探头(Transonic systems T206)记录肠系膜血流量(MBF)。通过激光多普勒血流仪(Periflux 2001 Master)估计微循环血流量(LDBF)。从全血中估计动静脉氧差(AVO2)(AVOXimeter 1000 E)。根据MBF和AVO2计算氧摄取量,并以毫升/分钟/100克组织表示。对有意识的动物进行慢性实验,将电极植入肠壁浆膜表面。在给予6-OHDA后1周、2周和3周进行肠道肌电参数测量。在颈部左迷走神经中用吸引电极记录迷走神经活动(在给予6-OHDA后1个月)。6-OHDA预处理在治疗后的第一周使主导慢波频率从0.62±0.10赫兹增加到0.74(±0.03)赫兹,增加了0.1赫兹(p<0.05)。在急性实验中慢波频率没有受到明显影响。在慢性实验中,初始增加后观察到慢波频率逐渐下降,28天后达到0.62±0.17赫兹的对照值。在慢性实验中给予6-OHDA后,慢波幅度没有观察到实质性变化。交感神经切除术后迷走神经中棘波活动的频率和幅度从7.96±1.3次/分钟增加到10.3±2次/分钟,从0.18±0.09毫伏增加到1.13±0.8毫伏。化学去神经支配分别使MBF和LDBF增加了18±3.6%和22±6.4%。与对照相比,肠道氧摄取量(VO2)增加了10.2±1.2%。与对照相比,心率和动脉压分别降低了18±4%和12±2.4%。肾上腺素能系统在调节大鼠肠道的肌电和运动活动中起着深远的作用。肾上腺素能神经元的持续活动会影响血管传导、毛细血管密度和氧扩散参数。