Langberg C W, Hauer-Jensen M, Sung C C, Kane C J
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205.
Radiother Oncol. 1994 Jul;32(1):29-36. doi: 10.1016/0167-8140(94)90446-4.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
调节肠道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，还经常发现炎性细胞聚集，特别是与急性或慢性黏膜溃疡相关时。这些炎性细胞是影响结缔组织代谢的细胞因子的主要来源。因此，细胞炎症反应与纤维化之间可能存在联系。这项临床前研究检测了分次照射对大鼠小肠中三种炎性/纤维化细胞因子表达的影响。采用大鼠肠转位模型对3 - 4厘米长的小肠段进行局部分次照射。59只雄性斯普拉格-道利大鼠接受9次每日剂量为5.2 Gy的照射或假照射。通过免疫组织化学评估白细胞介素1α（IL - 1α）、转化生长因子β1（TGF - β1）和血小板衍生生长因子 - AA（PDGF - AA）的表达。在照射完成后24小时、14天和26周检查照射和未照射的肠道。未照射的肠道显示IL - 1α、TGF - β1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。照射后的肠道在所有评估时间点均显示这三种细胞因子的表达增加。细胞因子表达增加与照射后肠道中的纤维化和炎性细胞浸润相关。这在有黏膜溃疡的区域尤为明显。小肠分次照射会在急性和慢性辐射损伤区域引起IL - 1α、TGF - β1和PDGF - AA表达增加。（摘要截短至250字）
