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表征Korl:ICR小鼠对洛哌丁胺诱导的便秘的反应。

Characterization the response of Korl:ICR mice to loperamide induced constipation.

作者信息

Kim Ji Eun, Yun Woo Bin, Sung Ji Eun, Lee Hyun Ah, Choi Jun Young, Choi Yeon Shik, Jung Young Suk, Kim Kil Soo, Hwang Dae Youn

机构信息

Department of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea.

Department of Biomedical Analysis, Korea Bio Polytechnic College, Nonsan, Korea.

出版信息

Lab Anim Res. 2016 Dec;32(4):231-240. doi: 10.5625/lar.2016.32.4.231. Epub 2016 Dec 23.

Abstract

Animal models of constipation induced with drugs and diet have been widely employed to investigate therapeutic effects and the action mechanism of drugs against this disease. ICR mice were selected to produce this disease model through oral administration of loperamide (Lop), even though SD rats are commonly utilized in studies of constipation. To compare the responses of ICR mice obtained from three different sources to constipation inducers, alterations in stool number, histopathological structure, mucin secretion and opioid-receptor downstream signaling pathway were measured in Korl:ICR (Korea FDA source), A:ICR (USA source) and B:ICR (Japan source) injected with low and high concentrations of Lop (LoLop and HiLop). The number, weight and moisture content of stools decreased significantly in the Lop treated group of all ICR relative to the Vehicle treated group. Additionally, decreased mucosa layer thickness, muscle thickness, and mucin secretion were observed in the transverse colon of Lop treated ICR mice, while a similar number of goblet cells and crypt of lieberkuhn were detected in the same group. Furthermore, a similar change in the level of Gα expression and PKC phosphorylation was detected in the Lop treated group relative to the vehicle treated group, while some differences in the change pattern were observed in the B:ICR group. Therefore, these results of the present study provide strong additional evidence that Korl:ICR, A:ICR and B:ICR derived from different sources have a similar overall response to constipation induced by Lop injection, although there were a few differences in the magnitude of their responses.

摘要

药物和饮食诱导的便秘动物模型已被广泛用于研究药物对该疾病的治疗效果及作用机制。尽管在便秘研究中通常使用SD大鼠,但本研究选择ICR小鼠,通过口服洛哌丁胺(Lop)来建立该疾病模型。为比较来自三种不同来源的ICR小鼠对便秘诱导剂的反应,对注射低浓度和高浓度Lop(LoLop和HiLop)的Korl:ICR(韩国食品药品监督管理局来源)、A:ICR(美国来源)和B:ICR(日本来源)小鼠,测量其粪便数量、组织病理学结构、粘蛋白分泌及阿片受体下游信号通路的变化。与溶剂处理组相比,所有ICR小鼠的Lop处理组粪便数量、重量和水分含量均显著降低。此外,在Lop处理的ICR小鼠横结肠中观察到粘膜层厚度、肌肉厚度和粘蛋白分泌减少,而在同一组中检测到杯状细胞和肠腺数量相似。此外,与溶剂处理组相比,Lop处理组中Gα表达水平和PKC磷酸化有类似变化,而在B:ICR组中观察到变化模式存在一些差异。因此,本研究的这些结果提供了有力的额外证据,表明来自不同来源的Korl:ICR、A:ICR和B:ICR对Lop注射诱导的便秘总体反应相似,尽管它们的反应程度存在一些差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54b2/5206230/326d6c804eda/lar-32-231-g001.jpg

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