Protective Effect of Urinary Trypsin Inhibitor on the Development of Radiation-Induced Lung Fibrosis in Mice
Protective Effect of Urinary Trypsin Inhibitor on the Development of Radiation-Induced Lung Fibrosis in Mice
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DOI：
10.1269/jrr.09108
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发表时间：
2010-05-01
影响因子：
2
通讯作者：
Nakano, Takashi
中科院分区：
文献类型：
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作者：
Katoh, Hiroyuki;Ishikawa, Hitoshi;Nakano, Takashi
本研究的目的是分析乌司他丁，尿胰蛋白酶抑制剂（UTI）。在肺损伤小鼠模型中抑制TGF-β信号通路和胸部照射诱导的肺纤维化用12戈伊或24戈伊的单次X射线剂量照射9周龄雌性纤维化敏感性C57 BL/6小鼠的胸部。以200.000单位/kg的剂量腹膜内给予Un，同时进行放射（同时UT！）或在照射后8-14天期间每天照射（RT UTI后）在照射后16周处死小鼠以评估肺纤维化的组织学分级和免疫组织化学TGF-β表达。还比较了给予24戈伊全肺+/- UTI的小鼠的存活率。RT UTI后降低了小鼠中肺纤维化的评分，但同时UTI对受辐射小鼠没有有益作用。RT后UTI小鼠的纤维化评分为32 +/-10，显著小于未经UTI治疗的辐射小鼠RT后UTI小鼠和RT组小鼠的TGF-β阳性细胞率分别为0.18 ± 0.03和0.23 ± 0.04，肝纤维化评分与TGF-β阳性率呈显著正相关（R-2 = 0 2 6，p < 0 0 1）。RT后UTI小鼠30周存活率明显高于单纯RT组（33% vs.10%）。p < 0.05）RT后给予UTI抑制TGF-β表达和辐射诱导的肺纤维化。这导致受辐射小鼠的存活时间显著延长，
This study aimed to analyze whether Ulinastatin, a urinary trypsin inhibitor (UTI). inhibits the TGF-beta signaling pathway and lung fibrosis induced by thoracic irradiation in a lung injury mouse model The thoraces of 9-week-old female fibrosis-sensitive C57BL/6 mice were irradiated with a single X-ray dose of 12 Gy or 24 Gy. urn was administrated intraperitoneally at a dose of 200.000 units/kg concurrently with radiation (concurrent UT!) or daily during the post-irradiation period for 8-14 days (post-RT UTI) Mice were sacrificed at 16 weeks alter irradiation to assess the histological grade of lung fibrosis and immunohistochemical TGF-beta expression Survival rates of mice given 24 Gy to the whole lung +/- UTI were also compared Post-RT UTI reduced the score of lung fibrosis in mice, but concurrent UTI had no beneficial effects in irradiated mice. The fibrosis score in post-RT UTI mice was 3 2 +/- 1 0, which was significantly smaller than that of irradiated mice without UTI treatment (RT alone, 6.0 +/- 1.3, p < 0 01) The rates of TGF-beta positive cells in post-RT UTI and the RT alone mice were 0 18 +/- 0 03 and 0.23 +/- 0 04, respectively (p < 0 01) There was a significantly positive correlation between the fibrosis score and the TGF-beta positive rate (R-2 = 0 26, p < 0 01) The survival rate at 30 weeks for post-RT UTI mice was significantly better than that of RT alone mice (33% vs. 10%. p < 0.05) The administration of post-RT UTI suppressed TGF-beta expression and radiation-induced lung fibrosis. which resulted in significant survival prolongation of the irradiated mice