Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury
Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury
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DOI：
10.1007/s10620-005-2926-9
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发表时间：
2005-09-01
影响因子：
3.1
通讯作者：
Lange, S
中科院分区：
文献类型：
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作者：
Abel, E;Ekman, T;Lange, S
细胞毒性治疗（磷酸依托泊苷，100 mg/kg体重[bw]，静脉注射[i. v.]）后4 - 48小时肠损伤使用结扎的肠袢在大鼠中进行了研究。铬-51乙二胺四乙酸（Cr-51-EDTA）和氯化铷-86（（RbCl）-Rb-86）沉积在管腔内，以确定肠通透性增加和离子通道破坏的程度。采用伊文思蓝（EB）检测内皮渗漏。记录肠道形态。内皮功能障碍，观察到的EB外渗增加，是明显的细胞毒性治疗后4小时。肠上皮损伤，观察到Cr-51-EDTA渗透增加和Rb-86吸收减少，48小时后发生。最后，组织学显示隐窝细胞增殖减少，Ki 67阳性细胞减少。研究结果表明，在细胞毒性治疗后肠损伤的发展中，内皮细胞破坏是早期事件，随后发生上皮功能障碍和隐窝干细胞停滞。这些知识可能对未来干预试验的设计具有重要意义。
Intestinal injury 4 - 48 hr after cytotoxic therapy ( etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid (Cr-51-EDTA) and rubidium-86 chloride ((RbCl)-Rb-86) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in Cr-51-EDTA permeation and a decrease in Rb-86 absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.