丙泊酚对卵清蛋白诱导的豚鼠哮喘舒张作用的研究。
Investigation of the relaxant effects of propofol on ovalbumin-induced asthma in guinea pigs.
作者信息
Bagcivan I, Cevit O, Yildirim M K, Gursoy S, Yildirim S, Kaya T, Mimaroglu C
机构信息
Cumhuriyet University School of Medicine, Department of Pharmacology, Sivas, Turkey.
出版信息
Eur J Anaesthesiol. 2007 Sep;24(9):796-802. doi: 10.1017/S0265021507000415. Epub 2007 May 22.
BACKGROUND AND OBJECTIVE
Because the incidence of asthma appears to be increasing, the importance of proper perioperative management of individuals with asthma will also continue to increase. Although its mechanism of smooth muscle relaxation is unknown, propofol has been associated with less bronchoconstriction during anaesthetic induction. The aim of this study was to investigate the possible mechanism of these effects and the effects of propofol on the isolated trachea preparations from control and ovalbumin-sensitized guinea pigs.
METHODS
Adult male guinea pigs, weighing 280-330 g, were randomly allocated to two experimental groups, each consisting of 10 animals. Ten guinea pigs were sensitized by intramuscular injections of 0.30 mL of a 5% (w/v) ovalbumin/saline solution into each thigh (0.6 mL total) on days 1 and 4, whereas the remaining 10 served as controls receiving a total of 0.6 mL distilled water on days 1 and 4 as placebo. The isolated trachea preparations were mounted in tissue baths with modified Krebs-Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. We tested the effects of propofol (10(-7)-10(-3) M) on resting tension and after precontraction with carbachol and histamine on isolated trachea preparations from control and ovalbumin-sensitized guinea pigs. We also tested the effect of propofol on isolated trachea preparations precontracted with carbachol and histamine in the absence and presence of different inhibitors or antagonists. We investigated propofol responses in tracheal smooth muscle precontracted with CaCl2.
RESULTS
Propofol (10(-7)-10(-3) M) produced a concentration-dependent relaxation of isolated tracheal preparations precontracted by carbachol (10(-6) M) and histamine (10(-6) M) in both groups. Preincubation with N(w)-nitro L-arginine methyl ester (3x10(-5) M), indomethacin (10(-5) M) or propranolol (10(-4) M) did not produce a significant alteration on propofol-induced relaxation responses (P>0.05), while preincubation with tetraethylammonium (3x10(-4) M) significantly decreased the propofol-induced relaxation responses in both groups (P<0.05). Propofol (10(-7)-10(-3) M) induced concentration-dependently relaxations in isolated trachea rings precontracted with CaCl2 in both the control and ovalbumin-sensitized groups.
CONCLUSION
Propofol induced concentration-dependent relaxations in precontracted, isolated trachea smooth muscle of guinea pigs in both the control and ovalbumin-sensitized groups. These relaxations were independent of epithelial function and stimulation of beta adrenergic receptors. Opened Ca2+-sensitive K+ channels and inhibited L-type Ca2+ channels can contribute to these relaxations.
背景与目的
由于哮喘的发病率似乎在上升，哮喘患者围手术期正确管理的重要性也将持续增加。尽管丙泊酚平滑肌松弛的机制尚不清楚，但在麻醉诱导期间，丙泊酚与较少的支气管收缩有关。本研究的目的是探讨这些作用的可能机制以及丙泊酚对来自对照和卵清蛋白致敏豚鼠的离体气管标本的影响。
方法
体重280 - 330 g的成年雄性豚鼠随机分为两个实验组，每组10只动物。10只豚鼠在第1天和第4天通过在每条大腿肌肉注射0.30 mL 5%（w/v）卵清蛋白/生理盐水溶液（共0.6 mL）进行致敏，而其余10只作为对照，在第1天和第4天共接受0.6 mL蒸馏水作为安慰剂。将离体气管标本安装在含有改良克雷布斯 - 亨塞尔特溶液的组织浴中，并用95%氧气和5%二氧化碳通气。我们测试了丙泊酚（10⁻⁷ - 10⁻³ M）对对照和卵清蛋白致敏豚鼠离体气管标本的静息张力以及用卡巴胆碱和组胺预收缩后的影响。我们还测试了丙泊酚在不存在和存在不同抑制剂或拮抗剂的情况下对用卡巴胆碱和组胺预收缩的离体气管标本的影响。我们研究了丙泊酚对用氯化钙预收缩的气管平滑肌的反应。
结果
丙泊酚（10⁻⁷ - 10⁻³ M）在两组中均使由卡巴胆碱（10⁻⁶ M）和组胺（10⁻⁶ M）预收缩的离体气管标本产生浓度依赖性舒张。用N⁺-硝基-L-精氨酸甲酯（3×10⁻⁵ M）、吲哚美辛（10⁻⁵ M）或普萘洛尔（10⁻⁴ M）预孵育对丙泊酚诱导的舒张反应没有产生显著改变（P>0.05），而用四乙铵（3×10⁻⁴ M）预孵育在两组中均显著降低了丙泊酚诱导的舒张反应（P<0.05）。丙泊酚（10⁻⁷ - 10⁻³ M）在对照和卵清蛋白致敏组中均使用氯化钙预收缩的离体气管环产生浓度依赖性舒张。
结论
丙泊酚在对照和卵清蛋白致敏组中均使预收缩的豚鼠离体气管平滑肌产生浓度依赖性舒张。这些舒张与上皮功能和β肾上腺素能受体的刺激无关。开放的钙敏感钾通道和抑制L型钙通道可导致这些舒张。
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