伊立替康损伤紧密连接并导致大鼠细菌易位。
Irinotecan injures tight junction and causes bacterial translocation in rat.
机构信息
Department of Surgery, Institute of Health Bioscience, University of Tokushima, Tokushima, Japan.
出版信息
J Surg Res. 2012 Apr;173(2):341-7. doi: 10.1016/j.jss.2010.10.003. Epub 2010 Nov 24.
BACKGROUND
Tight junctions are an essential component of intestinal epithelial barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The purpose of this study was to investigate whether irinotecan induces bacterial translocation in rats, and thus elucidate the relationship between tight junction and bacterial translocation.
METHODS
Ten rats were divided into two groups: Five were treated with irinotecan and five were not treated with irinotecan, the control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis. Controls were treated with a saline solution.
RESULTS
In eighty percent of irinotecan treated rats, bacteria were detected in the mesenteric lymph node or spleen. Large intestinal resistance of the rats was decreased. On the contrary, small intestinal resistance increased. Claudin-1 protein expression of both the small and large intestine decreased (P < 0.05), occludin protein expression of the small intestine decreased (P < 0.05), and occludin protein expression of the large intestine had decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05).
CONCLUSIONS
Irinotecan injures claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier and induces bacterial translocation.
背景
紧密连接是肠道上皮屏障的重要组成部分。 Claudin-1、occludin 和 ZO-1 是紧密连接的组成部分。本研究旨在探讨伊立替康是否会引起大鼠细菌易位，并阐明紧密连接与细菌易位的关系。
方法
将 10 只大鼠分为两组：5 只给予伊立替康，5 只作为对照组不给予伊立替康。伊立替康处理组大鼠在第 0 和 1 天腹腔内给予伊立替康 250mg/kg，然后在治疗后 48 小时处死，收集组织进行分析。对照组给予生理盐水处理。
结果
在 80%的伊立替康处理大鼠中，肠系膜淋巴结或脾脏中检测到细菌。大鼠的大肠阻力降低，而小肠阻力增加。相反，小 肠和大肠的 Claudin-1 蛋白表达均降低（P<0.05），小肠的 occludin 蛋白表达降低（P<0.05），大肠的 occludin 蛋白表达呈下降趋势（P=0.07）。在伊立替康处理的大鼠中，小肠 Claudin-1 mRNA 减少（P<0.05），大肠 Claudin-1 mRNA 有减少趋势（P=0.05），小 肠和大肠的 occludin mRNA 均减少（P<0.05）。
结论
伊立替康损伤 Claudin-1 和 occludin，导致肠道上皮屏障功能障碍，引起细菌易位。
Zotero 插件