Shi Yanyan, Zhang Yu, Zhao Fangying, Ruan Hua, Huang Honghui, Luo Lingfei, Li Li
1] The State Key Laboratory Breeding Base of Bioresources and Eco-environments, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China [2].
The State Key Laboratory Breeding Base of Bioresources and Eco-environments, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China.
Sci Rep. 2014 Jul 7;4:5602. doi: 10.1038/srep05602.
The mechanisms underlying gut development, especially peristalsis, are widely studied topics. However, the causes of gut peristalsis-related diseases, especially Opioid-Induced Bowel Dysfunction (OIBD) disorder, have not been well defined. Therefore, our study used zebrafish, a popular model for studying both gut development and peristalsis, and DCFH-DA, a dye that clearly labels the live fish gut lumen, to characterize the formation process of gut lumen as well as the gut movement style in vivo. By applying Loperamide Hydrochloride (LH), the μ-opioid receptor-specific agonist, we established an OIBD-like zebrafish model. Our study found that acetylcholine (ACh) was a key transmitter that derepressed the phenotype induced by LH. Overall, the study showed that the antagonistic role of ACh in the LH-mediated opioid pathway was evolutionarily conserved; moreover, the OIBD-like zebrafish model will be helpful in the future dissection of the molecular pathways involved in gut lumen development and pathology.
肠道发育的潜在机制,尤其是蠕动,是广泛研究的课题。然而,肠道蠕动相关疾病的病因,尤其是阿片类药物引起的肠道功能障碍(OIBD),尚未得到明确界定。因此,我们的研究使用斑马鱼(一种常用于研究肠道发育和蠕动的模型)和DCFH-DA(一种能清晰标记活鱼肠道内腔的染料)来表征体内肠道内腔的形成过程以及肠道运动方式。通过应用μ-阿片受体特异性激动剂盐酸洛哌丁胺(LH),我们建立了一种类似OIBD的斑马鱼模型。我们的研究发现乙酰胆碱(ACh)是解除LH诱导表型抑制的关键递质。总体而言,该研究表明ACh在LH介导的阿片类途径中的拮抗作用在进化上是保守的;此外,类似OIBD的斑马鱼模型将有助于未来剖析参与肠道内腔发育和病理的分子途径。