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使用 DECRO 系统对群居大鼠进行无创有套遥测,以综合评估呼吸系统、心电图和活动。

Non invasive jacketed telemetry in socially-housed rats for a combined assessment of respiratory system, electrocardiogram and activity using the DECRO system.

机构信息

Etisense SAS, 60A Avenue Rockefeller, 69008 Lyon, France.

Charles River Laboratories France Safety Assessment SAS, Department of Safety Pharmacology, 329, Impasse du Domaine Rozier, 69210 Saint Germain-Nuelles, France.

出版信息

J Pharmacol Toxicol Methods. 2022 Sep-Oct;117:107195. doi: 10.1016/j.vascn.2022.107195. Epub 2022 Jun 30.

Abstract

Respiratory and cardiovascular systems are among the vital organ systems that should be studied in safety pharmacology core battery test. Non-invasive jacketed external telemetry technology that enables concomitant monitoring of both systems has been available and used widely for non-rodent species. Recently, the DECRO system, a miniaturized technology system in line with the "3Rs" principles, has been developed to provide a similar approach in rats. However, data to evaluate this system in socially-housed rats is lacking. Therefore, the objectives of this study were to determine the tolerability and the material integrity of this novel solution in pair-housed rats in two conditions: i) in a single session of 22 h simulating a stand-alone safety pharmacology study design, and ii) in three repeated sessions of 22 h each, simulating the inclusion of safety pharmacology endpoints in a 1-month toxicology study. In both conditions, the GABA receptor agonist baclofen was used as a reference compound inducing cardiorespiratory changes. Our results provided evidence that this novel solution was well tolerated, the material was resistant to deterioration and that it allowed the accurate recording, in a non-invasive manner, of cardiorespiratory parameters and activity level in freely moving, pair-housed rats in the above two conditions. In addition, the expected respiratory depressant effects of baclofen were recorded. These results pave the way for considering this novel solution as an enhanced approach for nonclinical safety assessment in rats.

摘要

呼吸系统和心血管系统是安全药理学核心电池测试中应该研究的重要器官系统之一。非侵入性带壳外部遥测技术能够同时监测这两个系统,已经广泛应用于非啮齿类动物。最近,一种符合“3R”原则的微型技术系统 DECRO 系统已经开发出来,为大鼠提供了类似的方法。然而,缺乏评估该系统在群居大鼠中应用的数据。因此,本研究的目的是确定在两种情况下,即:i)在模拟独立安全药理学研究设计的 22 小时单次实验中,以及 ii)在模拟在 1 个月毒性研究中包含安全药理学终点的三次重复 22 小时实验中,这种新型解决方案在成对饲养大鼠中的耐受性和材料完整性。在这两种情况下,GABA 受体激动剂巴氯芬被用作诱导心肺变化的参考化合物。我们的研究结果表明,这种新型解决方案具有良好的耐受性,材料不易损坏,可以非侵入性地准确记录自由活动的成对饲养大鼠在上述两种情况下的心肺参数和活动水平。此外,还记录到了巴氯芬预期的呼吸抑制作用。这些结果为考虑这种新型解决方案作为大鼠非临床安全性评估的增强方法铺平了道路。

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