Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats
Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats
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DOI：
10.1080/110241502321116541
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Tanaka, K
中科院分区：
文献类型：
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作者：
Doi, K;Horiuchi, T;Tanaka, K
目的：探讨新型重组中性粒细胞弹性蛋白酶抑制剂 ONO-5046 Na 在大鼠中减少缺血再灌注引起的肝转移的可能性。设计：实验室实验研究。地点：研究实验室，日本。受试者：雄性 Fischer 大鼠。干预措施：对大鼠进行 60 分钟的 70% 部分肝缺血，然后将大鼠结肠腺癌细胞 (RCN-H4) 注射到大鼠体内。脾脏。将动物分为两个测试组和一个对照组。一组以 10 毫克/公斤/小时的速度静脉注射 ONO-5046 Na。第二组同期给予生理盐水，对照组不缺血。主要观察指标：接种三周后，计数肝脏表面肿瘤结节的数量。通过单四唑试验测定ONO-5046 Na的抗癌作用。结果：肝脏缺血再灌注增加了夹闭和未夹闭肝叶中RCN-H4肝转移的数量。 ONO-5046 Na 在未钳夹的肝叶中显着抑制这种作用，但没有抗癌作用。结论：中性粒细胞弹性蛋白酶可能在缺血再灌注导致的血源性肝转移增加中发挥重要作用，特别是在未钳夹的肝叶中。
Objective: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion.Design: Laboratory experimental study.Setting: Research laboratory, Japan.Subjects: Male Fischer rats.Interventions: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic.Main outcome measures: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay.Results: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect.Conclusion: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.