Department of Radiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Mol Med Rep. 2013 Apr;7(4):1091-5. doi: 10.3892/mmr.2013.1318. Epub 2013 Feb 8.
The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation‑induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.
本研究旨在探讨中性粒细胞弹性蛋白酶(NE)抑制剂西维来司他能否减轻小鼠放射性肺损伤。将 C57BL/6J 小鼠的双侧全肺接受 20Gy 照射。RE2 组在照射前和照射后 1 小时给予西维来司他,RE4 组在照射前和照射后 1、3 和 6 小时给予西维来司他。R 组接受照射但不给予西维来司他注射。未给予西维来司他注射或照射的小鼠作为对照。在照射后 24 和 48 小时测量 NE 活性,并在照射后 24 小时、48 小时和 15 周处死小鼠进行组织病理学检查。在 RE2 和 RE4 组中,与 R 组相比,NE 活性在照射后 48 小时内显著受到抑制。在组织病理学检查期间对每组的肺损伤程度进行评分。结果表明,照射后 15 周,RE2 和 RE4 组的评分明显低于 R 组。综上所述,西维来司他通过抑制 NE 活性和过度炎症反应减轻了小鼠的放射性肺损伤。