Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism
Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism
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DOI：
10.1016/s0016-5085(00)70363-5
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发表时间：
2000-06-01
期刊：
影响因子：
29.4
通讯作者：
Stenson, WF
中科院分区：
文献类型：
--
作者：
Riehl, T;Cohn, S;Stenson, WF
背景与目的：骨髓和肠道是放射性损伤的主要部位。在肠或骨髓中对辐射损伤的细胞反应可以通过在辐射之前给予的药剂来调节。已知脂多糖在骨髓中具有辐射防护作用，但其对肠道的影响尚不清楚，我们试图确定脂多糖在肠道中是否具有辐射防护作用，如果是，则确定其辐射防护作用的机制。研究方法：用肠外脂多糖或溶剂处理小鼠，然后照射（在铯照射器中进行14戈伊全身照射），使用克隆形成测定法在照射后3.5天评估存活的肠隐窝数。结果：在照射前2-24小时肠外给予脂多糖导致在照射后3.5天存活的肠隐窝数增加2倍。脂多糖的辐射防护作用可以通过同时给予选择性环氧合酶2抑制剂来消除，脂多糖在野生型小鼠中具有辐射防护作用，但在环氧合酶2破坏的小鼠中不具有辐射防护作用，脂多糖的胃肠外给药导致肠中野牡丹素的产生增加，并诱导上皮下成纤维细胞和绒毛中环氧合酶2的表达，但不诱导隐窝中环氧合酶2的表达，上皮细胞结论：脂多糖对小鼠肠道具有辐射防护作用，其机制可能是通过胰高血糖素依赖性途径实现的。
Background & Aims: The bone marrow and the intestine are the major sites of radiation-induced injury. The cellular response to radiation injury in the intestine or bone marrow can be modulated by agents given before irradiation. Lipopolysaccharide is known to be radioprotective in the bone marrow, but its effect on the intestine is not known, We sought to determine if lipopolysaccharide is radioprotective in the intestine and, if so, to determine the mechanism of its radioprotective effects. Methods: Mice were treated with parenteral lipopolysaccharide or vehicle and then irradiated (14 Gy total body irradiation in a cesium irradiator), The number of surviving intestinal crypts was assessed 3.5 days after irradiation using a clonogenic assay, Results: Parenteral administration of lipopolysaccharide 2-24 hours before irradiation resulted in a 2-fold increase in the number of surviving crypts 3.5 days after irradiation. The radioprotective effects of lipopolysaccharide could be eliminated by coadministration of a selective inhibitor of cyclooxygenase 2, Lipopolysaccharide was radioprotective in wild-type mice but not in mice with a disrupted cyclooxygenase 2, Parenteral administration of lipopolysaccharide resulted in increased production of prostaglandins in the intestine and in the induction of cyclooxygenase 2 expression in subepithelial fibroblasts and in villous, but not crypt, epithelial cells. Conclusions: Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-dependent pathway.