^(60)Co外照射对大鼠5-氟尿嘧啶血胰屏障通透性的影响

Effect of radiotherapy on penetration of 5-FU in blood-pancreatic barrier in rats

目的 探讨胰腺癌综合治疗中不同剂量放射治疗对于化学治疗疗效可能产生的影响。方法 采用高效液相色谱法 (HPLC)分别测定了大白鼠经60 Co胰腺外照射 0、2、10、2 0、30、40Gy后 8h ,静注 5 氟尿嘧啶 (5 FU) (93.75mg·kg-1)在胰腺组织中的穿透比 (PR)。同行胰腺病理检查。结果 5 FU在大鼠胰腺组织中的穿透比在小剂量 (2Gy)放疗后 8h较对照组明显升高。在大剂量放疗 (≥ 10Gy)后 8h ,PR随放疗剂量的增加而增加 (相关系数r=0 .99) ,但PR均低于或与正常对照组差异无显著意义 (P <0 .0 5 )。且在 2 0Gy剂量组中胰岛细胞已出现部分退化、变性。结论 分次治疗常用剂量(2Gy)放疗后 ,同时加用化疗 ,5 FU在胰腺组织中穿透比明显升高 ,可能会取得较好的化疗效果 ,二者具协同作用。中、大剂量放疗时 (≥ 10Gy) ,急性期合并化疗 ,放射治疗在一定程度上可能会降低血胰屏障对 5 FU的通透性 ,影响化学治疗的效果。大剂量放疗时 (2 0Gy) ,急性期即可出现胰岛细胞损伤。

Objective To investigate the effect of radiotherapy dose on penetration of 5 FU (5 fluorouracil) in blood pancreatic barrier in rats. Methods After the pancreatic region of the rats were irradiated by 2, 10, 20, 30 and 40 (Gy) doses of γ ray , we investigated the penetration ratio (PR) of 5 FU in the pancreatic tissue with HPLC assay. Results When treated with low dose of γ ray (2 Gy), the PR of 5 FU increased obviously after 8 hours. But in the high dose groups (≥10 Gy), the PR was less than or had no difference with control group. At the same time, we found that the islets had appeared pathological degeneration, while the pancreatic lobular structure, acini and ducts had no visible changes in 20 Gy group. Conclusions After the treatment of low dose of γ ray combined with 5 FU, the effect of chemoradiotherapy may be improved for enhanced PR of 5 FU in pancreatic tissue, and at the same time, chemotherapy and radiotherapy cooperate with each other. But in high dose groups(≥10 Gy), radiotherapy may reduce the effect of chemotherapy in acute phase. After high dose radiotherapy, we should pay attention to the change of glucose resistance of patient to reduce the incidence of radiotherapy complication.