Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds
Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds
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DOI：
10.1097/00000539-199910000-00039
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发表时间：
1999-10-01
影响因子：
5.7
通讯作者：
Laster, MJ
中科院分区：
文献类型：
--
作者：
Sonner, JM;Gong, D;Laster, MJ
在这项研究中，我们测量了最低肺泡麻醉剂浓度（MAC）在几个小鼠品系，包括用于构建基因工程小鼠的品系。这一点很重要，因为定义的遗传修饰越来越多地用于测试吸入麻醉剂作用的机制，MAC的背景变异性可能会影响这些研究的解释。我们研究了应变对地氟烷、异氟烷、氟烷、乙醇、实验麻醉剂1-氯-1，2，2-三氟环丁烷和非固定剂1，2-二氯六氟环丁烷的惊厥50%有效剂量（在50%的动物中产生惊厥所需的剂量）的MAC的影响。这些药物在8个近交系中进行了研究，包括实验室和野生小鼠品系（129/J、129/SvJ、129/奥拉Hsd、C57 BL/6 NHsd、C57 BL/6 J、DBA/2 J、Spret/Ei和Cast/Ei）、一个杂交品系（B6129 F2/J，源自C57 BL/6 J和129/J品系）和一个远交品系（CD-1）。为了测试我们在转基因小鼠中检测效应的能力，我们将这些数据与缺乏蛋白激酶C基因（PKC γ）的γ（神经元）亚型的小鼠的数据进行了比较。我们还评估了切断小鼠的尾尖（获得用于遗传分析的组织的标准方法）是否增加了MAC（例如，通过脊髓的致敏作用）。MAC和惊厥剂50%有效剂量值在菌株之间略有不同，使用常规麻醉剂时MAC的最低值至最高值范围为17%至39%，使用实验麻醉剂1-氯-1，2，2-三氟环丁烷时高达48%。对非固定剂的惊厥变化为47%。切断尾尖不影响MAC PKC γ基因敲除小鼠的MAC值显著高于异氟烷对照动物，但氟烷或地氟烷的MAC值不显著高于对照动物，这意味着PKC γ引起的蛋白磷酸化可改变对异氟烷的敏感性。意义：麻醉效力在近交系、远交系、野生系和实验室小鼠品系之间有适度的差异。神经形式的蛋白激酶C的缺乏增加了异氟烷的最低肺泡麻醉剂浓度，表明蛋白激酶C（PKC γ）的γ-亚型的蛋白磷酸化可以影响这种麻醉剂的效力。
In this study, we measured the minimum alveolar anesthetic concentration (MAC) in several mouse strains, including strains used in the construction of genetically engineered mice. This is important because defined genetic modifications are used increasingly to test mechanisms of inhaled anesthetic action, and background variability in MAC can potentially influence the interpretation of these studies. We investigated the effect of strain on MAC for desflurane, isoflurane, halothane, ethanol, the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane, and convulsive 50% effective dose (the dose required to produce convulsions in 50% of animals) of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane. These drugs were studied in eight inbred strains, including both laboratory and wild mouse strains (129/J, 129/SvJ, 129/Ola Hsd, C57BL/ 6NHsd, C57BL/6J, DBA/2J, Spret/Ei, and Cast/Ei), one hybrid strain (B6129F2/J, derived from the C57BL/6J and 129/J strains), and one outbred strain (CD-1). To test our ability to detect effects in a genetically modified mouse, we compared these data with those for a mouse lacking the gamma (neuronal) isoform of the protein kinase C gene (PKC gamma). We also assessed whether amputating the tail tip of mice (a standard method of obtaining tissue for genetic analysis) increased MAC (e.g., by sensitization of the spinal cord). MAC and convulsant 50% effective dose values differed modestly among strains, with a range of 17% to 39% from the lowest to highest values for MAC using conventional anesthetics, and up to 48% using the experimental anesthetic 1-chloro-1,2,2-trifluorocyclobutane. Convulsivity to the nonimmobilizer varied by 47%. Amputating the tail tip did not affect MAC PKC gamma knockout mice had significantly higher MAC values than control animals for isoflurane, but not for halothane or desflurane, which implies that protein phosphorylation by PKC gamma can alter sensitivity to isoflurane. Implications: Anesthetic potency differs by modest amounts among inbred, outbred, wild, and laboratory mouse strains. Absence of the neural form of protein kinase C increases minimum alveolar anesthetic concentration for isoflurane, indicating that protein phosphorylation by the gamma-isoform of protein kinase C (PKC gamma) can influence the potency of this anesthetic.