Bekusova Viktoria V, Falchuk Evgeny L, Okorokova Larisa S, Kruglova Natalia M, Nozdrachev Alexander D, Markov Alexander G
Department of Physiology, St. Petersburg State University, St. Petersburg 197183, Russia.
I.P.Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg 199034, Russia.
Cancer Biol Med. 2018 Aug;15(3):251-259. doi: 10.20892/j.issn.2095-3941.2018.0016.
The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending colon. Inflammatory bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine (DMH)-induced colon adenocarcinoma.
The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical microscopy.
Rats with DMH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however, the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier function.
The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their barrier function.
近端和远端大肠的形态和功能不尽相同。这些区域结直肠癌的发病率也存在差异，肿瘤更多出现在降结肠而非升结肠。炎症性肠病和结直肠癌会增加经上皮通透性，这是肠屏障功能降低的一个迹象。然而，尚无足够证据证实近端和远端结肠结直肠癌发病率的差异与肠通透性之间存在关联，或者致癌作用对结肠不同区域屏障特性的影响。本研究的目的是根据一种已开发的测绘方法，评估健康大鼠以及经1,2 - 二甲基肼（DMH）诱导的结肠腺癌大鼠大肠不同节段的通透性。
在尤斯灌流小室中检测雄性Wistar大鼠大肠壁的短路电流、跨上皮电阻以及对荧光素的细胞旁通透性。通过分光光度法分析从浆膜侧溶液的光密度，以评估从黏膜扩散至浆膜的荧光素浓度。通过光学显微镜进行形态计量学和组织学研究。
DMH诱导的结肠腺癌大鼠在肿瘤发生区域的跨上皮电阻升高。相比之下，肿瘤相邻区域的电生理特性没有变化，然而，与对照大鼠相比，这些区域对荧光素的细胞旁通透性增加，且其屏障功能明显降低。
结肠的屏障特性因肿瘤位置而异。肿瘤的通透性低于完整肠壁，可能通过破坏肿瘤相邻组织的屏障功能对其产生负面影响。
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