EXPRESSION OF FIBROGENIC CYTOKINES IN RAT SMALL-INTESTINE AFTER FRACTIONATED-IRRADIATION
EXPRESSION OF FIBROGENIC CYTOKINES IN RAT SMALL-INTESTINE AFTER FRACTIONATED-IRRADIATION
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DOI：
10.1016/0167-8140(94)90446-4
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发表时间：
1994-07-01
影响因子：
5.7
通讯作者：
KANE, CJM
中科院分区：
文献类型：
--
作者：
LANGBERG, CW;HAUERJENSEN, M;KANE, CJM
调节肠道中辐射诱导纤维化反应的分子和细胞机制尚不清楚。除了结缔组织数量增加外，还经常发现炎症细胞聚集，特别是与急性或慢性粘膜溃疡相关。这些炎症细胞是影响结缔组织代谢的细胞因子的主要来源。因此，细胞炎症反应和纤维化之间可能存在联系。这项临床前研究检查了分段照射对大鼠小肠中三种炎症/纤维化细胞因子表达的影响。使用大鼠肠转位模型对一段 3-4 厘米的小肠进行局部分段照射。 59 只雄性 Sprague-Dawley 大鼠每天接受 9 次 5.2 Gy 的辐射或假辐射。通过免疫组织化学评估白细胞介素 1 α (IL-1 α)、转化生长因子 β 1 (TGF-β 1) 和血小板衍生生长因子-AA (PDGF-AA) 的表达。照射完成后24小时、14天和26周检查照射和未照射的肠道。未照射的肠道表现出 IL-1 α、TGF-β 1 和 PDGF-AA 的免疫组织化学表达，符合正常组织中已知的染色模式。受辐射的肠道在所有评估时间均显示所有三种细胞因子的表达增加。细胞因子表达增加与受辐射肠道中的纤维化和炎症细胞浸润相关。这在有粘膜溃疡的区域尤其明显。小肠分次照射会导致急性和慢性放射损伤区域 IL-1 α、TGF-β 1 和 PDGF-AA 的表达增加。照射后 24 小时至 26 周期间，这些纤维形成细胞因子的表达持续增加，表明在照射时启动了一个活跃的持续过程。
The molecular and cellular mechanisms that regulate the radiation-induced fibrotic response in the intestine are not known. In addition to increased amounts of connective tissue, inflammatory cell aggregates are often found, especially in conjunction with acute or chronic mucosal ulcerations. These inflammatory cells are a major source of cytokines that influence connective tissue metabolism. Hence, a possible link may exist between the cellular inflammatory response and fibrosis. This preclinical study examined the influence of fractionated irradiation on the expression of three inflammatory/fibrogenic cytokines in rat small intestine. A rat intestinal transposition model was used for localized fractionated irradiation of a 3-4-cm segment of small bowel. Fifty-nine male Sprague-Dawley rats were irradiated or sham irradiated with 9 daily fractions of 5.2 Gy. Expression of Interleukin 1 alpha (IL-1 alpha), Transforming growth factor beta 1 (TGF-beta 1), and Platelet derived growth factor-AA (PDGF-AA) was assessed by immunohistochemistry. Irradiated and unirradiated intestine was examined 24 h, 14 days, and 26 weeks after completion of irradiation. Unirradiated intestine exhibited immunohistochemical expression of IL-1 alpha, TGF-beta 1 and PDGF-AA that conformed to known staining patterns in normal tissue. Irradiated intestine showed increased expression of all three cytokines at all assessment times. The increased cytokine expression correlated with fibrosis and inflammatory cell infiltrates in irradiated intestine. This was particularly evident in areas with mucosal ulcerations. Fractionated irradiation of small intestine elicits increased expression of IL-1 alpha, TGF-beta 1, and PDGF-AA in areas of acute and chronic radiation injury. The sustained increase in expression of these fibrogenic cytokines from 24 h to 26 weeks after irradiation suggests an active ongoing process that is initiated at the time of irradiation.