权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Biological study on Prevention of Restenosis by Intra-arterial Irradiation

动脉内照射预防再狭窄的生物学研究

基本信息

批准号：
10470193
负责人：
SHIBUYA Hitoshi
金额：
$ 1.47万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470193/
关键词：
restenosis smooth muscle cells PCNA ionizing radiation smooth muscle cell

项目摘要

The purpose of this study was to pursue the biological mechanisms by which ionizing radiation (IR) inhibits intimal hyperplasia after PTA. Since it is already known that growth inhibition of smooth muscle cells is a major factor of the phenomenon, we used primary cultured smooth muscle cells as a model. When cells were X-irradiated at a dose of 20 Gy, no apparent evidence of poptosis was obtained in terms of morphology at least up to 48h. None of enhanced expression of Fas or Fas-L, or activation of caspase-8 was observed following irradiation. Furthermore, cleavage of PKC-δ was not detected, indicating that apoptotic activities in smooth muscle cells following irradiation is quite low. It was thus suggested that apoptosis does not seem to be attributed to the IR-induced growth inhibition of smooth muscle cells. We found that PCNA-dependent DNA repair is functional in smooth muscle cells following X-irradiation and showed that another base excision repair (BER) pathway, pol β-dependent one, is not functional under the condition. These results strongly imply that PCNA-dependent DNA repair may be important to get apoptosis-refractory properties in smooth muscle cells. We also showed radiobiological properties of osteoradionercrosis (ORN) of the mandibular bone, which is caused by vessel damage in the bone, utilizing clinical data from pataients receiving Ir brachytherapy for oral tongue carcinoma. Cox proportional regression analysis revealed that biological effective dose (BED) using an α/β ratio for late responding tissues estimated at the surface of the lower lingual gum was the best prognosticator to predict ORN, and dose-response curves for ORN were obtained. These results provide useful information to analyze inhibitory effects of restenosis by intra-arterial irradiation.

本研究的目的是探讨电离辐射（IR）抑制PTA后内膜增生的生物学机制。由于已经知道平滑肌细胞的生长抑制是该现象的主要因素，因此我们使用原代培养的平滑肌细胞作为模型。当以20戈伊的剂量对细胞进行X射线照射时，至少长达48小时的形态学上没有获得明显的三元共聚物的证据。照射后未观察到Fas、Fas-L表达增强或caspase-8活化。此外，未检测到PKC-δ裂解，表明照射后平滑肌细胞的凋亡活性相当低。因此，这表明，细胞凋亡似乎并不归因于IR诱导的平滑肌细胞的生长抑制。我们发现PCNA依赖的DNA修复在X射线照射后的平滑肌细胞中是功能性的，并且表明另一个碱基切除修复（BER）途径，pol β依赖的途径，在该条件下不起作用。这些结果强烈暗示PCNA依赖的DNA修复可能对平滑肌细胞获得抗凋亡特性很重要。我们还显示了放射性骨坏死（ORN）的放射生物学特性，这是由血管损伤引起的骨，利用临床数据从患者接受Ir近距离放射治疗口腔舌癌。考克斯比例回归分析表明，采用下舌面迟发反应组织的α/β比值估算的生物有效剂量（BED）是预测ORN的最佳指标，并得到了ORN的剂量-反应曲线。这些结果为分析动脉内照射对再狭窄的抑制作用提供了有用的信息。