Local Drug Delivery of ONO-4007 Inhibits Neointimal Hyperplasia in Dogs.

ONO-4007 的局部给药可抑制狗的新内膜增生。

• 批准号: 10670680
• 负责人: WAKIDA Yasushi
• 金额: $ 1.98万
• 依托单位: AICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670680/
• 关键词: LOCAL DRUG DELIVERY; RESTENOSIS; APOPTOSIS; ONO-4007; デリバリーバルーン; デリバルーンバルーン

ONO-4007 is a potent antineoplastic drug, which induces apoptosis in neoplastic cell. The aim of this study was whether facilitation of apoptosis in neointima after vascular injury could inhibit restenosis process by local ONO-4007 delivery. Methods : In eight dogs(13.2±2.2kg)bilateral femoral arteries were injured by three times 30 sec balloon inflation of PTCA catheter, which balloon size was 1.3〜1.5 times as large as the artery. In one side, ONO-4007(0.05mg or 0.5mg, n=4 in each group)was delivered by a microporous infusion catheter. In the other side saline was delivered as a control. Two or four weeks after balloon injury, the femoral arteries were resected and prepared for histological examination. Results : Total vassel area(VA)and medial area/VA did not differ between the groups. At four weeks, the intimal area/VA was significantly reduced in 0.5mg sites(2.75±1.06%)compared with the control sites(6.42±3.42%). Maximum neointimal thickness were significantly thinner in the treatment sites(0.05mg group, 65.5±64.4μm ; 0.5mg group, 50.5±21.7μm)than that in the control sites(128±104μm). At two weeks, Tunnel positive cells rate in the neointima were significantly increased in the treatment sites(71.4±14.1% vs 12.9±5.3%). Conclusion : These data indicate facilitation of apoptosis in the injured vassel by local ONO-4007 delivery inhibits neointimal hyperplasia in dog's femoral artery.

ONO-4007是一种有效的抗肿瘤药物，可诱导肿瘤细胞凋亡。本研究的目的是探讨ONO-4007局部给药对血管损伤后新生内膜凋亡的促进作用是否能抑制再狭窄的发生。研究方法：8只犬（13.2±2.2kg），经皮冠状动脉腔内成形术（PTCA）导管球囊扩张3次，每次30秒，球囊尺寸为动脉的1.3〜1.5倍，造成双侧股动脉损伤。在一侧，通过微孔输液导管递送ONO-4007（0.05mg或0.5mg，每组n=4）。在另一侧输送生理盐水作为对照。球囊损伤后2周或4周，切除股动脉并准备进行组织学检查。结果：总血管面积（VA）和内侧面积/VA在组间无差异。4周时，与对照部位（6.42±3.42%）相比，0.5mg部位（2.75±1.06%）的内膜面积/VA显著降低。治疗部位的最大新生内膜厚度（0.05 mg组，65.5±64.4μm ; 0.5 mg组，50.5±21.7μm）显著薄于对照部位（128±104μm）。两周时，治疗部位新生内膜中的Tunnel阳性细胞率显著增加（71.4±14.1% vs 12.9±5.3%）。结论：这些数据表明通过局部ONO-4007递送促进损伤血管中的细胞凋亡抑制了狗股动脉中的新生内膜增生。