Effects of okadaic acid on rat colon
Effects of okadaic acid on rat colon
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DOI：
10.1023/a:1026658921369
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发表时间：
1998-11-01
影响因子：
3.1
通讯作者：
Seino, Y
中科院分区：
文献类型：
--
作者：
Hosokawa, M;Tsukada, H;Seino, Y
本文观察了冈田酸（OA）对大鼠结肠粘膜损伤的影响。将OA喷洒在大鼠结肠粘膜上，用电子内窥镜系统观察，并将OA应用于体内显微镜视野。用Ussing电压钳技术测定OA引起的跨上皮电导（G（t））的变化。通过内窥镜观察，OA（60 nmol/kg）的腔内喷洒在粘膜下小静脉中引起短暂的微血栓，随后是粘膜水肿。内窥镜观察后的组织学研究显示粘膜下液体潴留，提示血管通透性增加。在体内显微镜下观察到微血栓形成。通过内窥镜观察后的电生理研究，加用和不加OA，基础G（t）值分别为54 +/- 6.2和36.2 +/- 4.2 mS/cm（2）（P < 0.01）。此外，在对照组大鼠中，血清中添加OA以浓度依赖性方式引起G（t）增加，而不增加乳酸脱氢酶的释放。2，4，6-Triaminopyrimidinium抑制OA诱导的G（t）变化达60%。这些结果表明，OA引起上皮细胞旁通透性的增加。我们的结论是，发达的微血栓是OA引起的粘膜损伤的第一个关键事件，其次是粘膜下小静脉和上皮细胞旁通路的渗透性增加。
Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (G(t)) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal G(t) values were 54 +/- 6.2 and 36.2 +/- 4.2 mS/cm(2), respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in G(t) in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced G(t) change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.