A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters
A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters
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DOI：
10.1016/j.ejphar.2004.04.024
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发表时间：
2004-06-16
影响因子：
5
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
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作者：
Sakaguchi, M;Takai, S;Miyazaki, M
我们评估了糜酶抑制剂2-（5-甲酰氨基-6-氧代-2-苯基-1，6-二氢嘧啶-1-基）-N-[{3，4-二氧代-1-苯基-7-（2-吡啶氧基）}-2-庚基]乙酰胺（NK 3201）是否抑制博莱霉素诱导的肺纤维化。仓鼠口服施用NK 3201（30 mg/kg/天）或安慰剂，在气管内滴注博来霉素（10 mg/kg）前5天开始。博莱霉素滴注后四周，安慰剂处理的仓鼠中的肺糜酶活性显著高于对照仓鼠，而NK 3201处理的仓鼠中的活性显著低于安慰剂处理的仓鼠。NK 3201给药仓鼠的纤维化面积与总面积的比值显著降低至安慰剂给药仓鼠的54.0%。因此，NK 3201可用于预防肺纤维化。(C)2004 Elsevier B. V.保留所有权利。
We evaluated whether a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]acetamide (NK3201), suppressed bleomycin-induced pulmonary fibrosis. Hamsters were orally administered NK3201 (30 mg/kg per day) or placebo, beginning 5 days before intratracheal instillation of bleomycin (10 mg/kg). Four weeks after the instillation of bleomycin, pulmonary chymase activity in placebo-treated hamsters was significantly higher than in control hamsters, whereas the activity in NK3201-treated hamsters was significantly lower than in placebo-treated hamsters. The ratio of fibrotic area to total area in NK3201-treated hamsters was significantly decreased to 54.0% of the ratio in placebo-treated hamsters. Therefore, NK3201 may be useful in the prevention of pulmonary fibrosis. (C) 2004 Elsevier B.V. All rights reserved.