Park Jae Hyung, Kwon Joong Goo, Kim Sun Joo, Song Dae Kyu, Lee Seok Guen, Kim Eun Soo, Cho Kwang Bum, Jang Byung Ik, Kim Dae Hwan, Sin Jeong-Im, Kim Tae Wan, Song In Hwan, Park Kyung Sik
Department of Physiology, Keimyung University School of Medicine, Daegu, Korea.
Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
J Neurogastroenterol Motil. 2015 Jan 1;21(1):51-61. doi: 10.5056/jnm14008.
BACKGROUND/AIMS: Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10(-/-)) mice.
Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining.
The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10(-/-) mice compared to IL-10(+/+) mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10(-/-) mice compared to IL-10(+/+) mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10(-/-) mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10(-/-) mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased.
These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.
背景/目的：炎症性肠病常伴有结肠运动障碍，并导致肠道平滑肌收缩性改变。在本研究中，使用从白细胞介素-10基因敲除（IL-10(-/-)）小鼠制备的平滑肌组织，研究慢性炎症状态下的结肠平滑肌收缩性。
将制备好的平滑肌切片置于器官浴系统中。使用卡巴胆碱以及添加L-硝基精氨酸甲酯（L-NAME）的电场刺激观察胆碱能和一氧化氮能神经元反应。通过免疫荧光染色观察Cajal间质细胞（ICC）网络、毒蕈碱受体、神经元型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）的表达。
与IL-10(+/+)小鼠相比，IL-10(-/-)小鼠近端和远端结肠的自发收缩性及ICC网络表达显著降低。与IL-10(+/+)小鼠相比，IL-10(-/-)小鼠近端结肠对卡巴胆碱的收缩反应显著降低，但在远端结肠未发现显著差异。此外，IL-10(-/-)小鼠近端结肠中2型毒蕈碱受体的表达降低。IL-10(-/-)小鼠近端和远端结肠在电场刺激后一氧化氮介导的舒张显著降低。在炎症结肠中，nNOS表达降低，而iNOS表达增加。
这些结果表明，近端和远端结肠中ICC网络和NOS系统的损伤，以及近端结肠中平滑肌胆碱能受体的损伤，可能在炎症结肠的运动障碍中起重要作用。
