Murillo Maria Del Pilar, Johansson Ebba, Bryntesson Victoria, Aronsson Patrik, Tobin Gunnar, Winder Michael, Carlsson Thomas
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Box 431, Gothenburg SE-40530, Sweden.
Gastroenterol Res Pract. 2023 Jan 27;2023:9090524. doi: 10.1155/2023/9090524. eCollection 2023.
Gastrointestinal dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD). The exact mechanisms behind these symptoms are not clearly understood. Studies in the well-established 6-hydroxydopamine (6-OHDA) lesioned rats of PD have shown altered contractility in isolated circular and longitudinal smooth muscle strips of distal colon. Contractile changes in proximal colon and distal ileum are nevertheless poorly studied. Moreover, segments may serve as better tissue preparations to understand the interplay between circular and longitudinal smooth muscle. This study aimed to compare changes in contractility between isolated full-thickness distal colon muscle strips and segments, and extend the investigation to proximal colon and distal ileum in the 6-OHDA rat model.
Spontaneous contractions and contractions induced by electrical field stimulation (EFS) and by the non-selective muscarinic agonist methacholine were investigated in strip and/or segment preparations of smooth muscle tissue from distal and proximal colon and distal ileum in an organ bath comparing 6-OHDA-lesioned rats with Sham-operated animals. . Our data showed increased contractility evoked by EFS and methacholine in segments, but not in circular and longitudinal tissue strips of distal colon after central 6-OHDA-induced dopamine denervation. Changes in proximal colon segments were also displayed in high K Krebs-induced contractility and spontaneous contractions.
This study further confirms changes in smooth muscle contractility in distal colon and to some extent in proximal colon, but not in distal ileum in the 6-OHDA rat model of PD. However, the changes depended on tissue preparation.
胃肠功能障碍是帕金森病(PD)最常见的非运动症状之一。这些症状背后的确切机制尚不清楚。在成熟的6-羟基多巴胺(6-OHDA)损伤的PD大鼠模型中进行的研究表明,远端结肠孤立的环形和纵形平滑肌条的收缩性发生了改变。然而,近端结肠和远端回肠的收缩变化研究较少。此外,肠段可能是更好的组织标本,有助于理解环形肌和纵形肌之间的相互作用。本研究旨在比较6-OHDA大鼠模型中孤立的全层远端结肠肌条和肠段之间的收缩性变化,并将研究扩展到近端结肠和远端回肠。
在器官浴槽中,比较6-OHDA损伤大鼠和假手术动物,研究远端和近端结肠以及远端回肠平滑肌组织的条带和/或肠段标本的自发收缩、电场刺激(EFS)诱导的收缩以及非选择性毒蕈碱激动剂乙酰甲胆碱诱导的收缩。我们的数据显示,在中枢6-OHDA诱导多巴胺去神经后,肠段中EFS和乙酰甲胆碱诱发的收缩性增加,但远端结肠的环形和纵形组织条带中未增加。近端结肠肠段的变化也表现在高钾Krebs诱导的收缩性和自发收缩中。
本研究进一步证实了6-OHDA大鼠PD模型中远端结肠平滑肌收缩性的变化,在一定程度上也证实了近端结肠的变化,但远端回肠未出现变化。然而,这些变化取决于组织标本。