Kallfass E, Krämling H J, Schultz-Hector S
GSF-Institut für Strahlenbiologie, Neuherberg, Germany.
Radiother Oncol. 1996 May;39(2):167-78. doi: 10.1016/0167-8140(96)01708-2.
The present immunohistochemical study of radiation-induced damage in major blood vessels is based on a multidisciplinary study (Schultz-Hector et al., Radiother. Oncol., 38: 205-214, 1996) investigating the combined effect of IORT of the coeliac axis and upper abdominal ERT. The paper describes the sequential changes occurring in the coeliac artery after IORT with 30 Gy, i.e. during and after combined IORT and fractionated ERT (total dose 40 Gy). Within 24 h after IORT, the arterial wall was found to be invaded by TNF-alpha positive macrophages, which later on disappeared within 7-14 days. At 2 days post-IORT, the medical smooth muscle cells were strongly positive for TNF-alpha and remained positive throughout the observation period of 63 days. At 80 days, a comparison of different IORT dose groups showed that TNF-alpha expression after 20 and 30 Gy IORT plus 40 Gy ERT had subsided, while it was still strongly evident after 40 Gy IORT. Negative reactions in sham irradiated animals or animals treated with ERT alone indicate that TNF-alpha expression was caused by IORT. After > 30 days post-IORT, there was increased collagen type I deposition in the adventitia. In two animals receiving the full ERT course, intimal proliferations involving mainly smooth muscle cells were observed. Our findings indicate that some features typical of radiation induced arteriosclerosis such as periarterial fibrosis and intimal proliferations can occur as early as < 60 days postirradiation. Macrophage invasion as well as TNF-alpha expression in medial smooth muscle cells are known to be important steps in the development of spontaneous atherosclerotic lesions. Therefore, early TNF-alpha induction in the arterial wall by a high local dose of X-irradiation may be regarded as one initiating factor of chronic radiation-induced arteriosclerosis.
目前关于大血管放射性损伤的免疫组织化学研究基于一项多学科研究(舒尔茨 - 赫克托等人,《放射肿瘤学》,38: 205 - 214, 1996),该研究调查了腹腔动脉轴术中放疗(IORT)与上腹部外照射放疗(ERT)的联合效应。该论文描述了在30 Gy的IORT后,即联合IORT和分次ERT(总剂量40 Gy)期间及之后,腹腔动脉中发生的一系列变化。在IORT后24小时内,发现动脉壁被肿瘤坏死因子-α(TNF-α)阳性巨噬细胞浸润,这些巨噬细胞随后在7 - 14天内消失。IORT后2天,血管中层平滑肌细胞TNF-α呈强阳性,并在整个63天的观察期内一直保持阳性。在80天时,不同IORT剂量组的比较显示,20 Gy和30 Gy IORT加40 Gy ERT后的TNF-α表达已经消退,而在40 Gy IORT后仍很明显。假照射动物或仅接受ERT治疗的动物中的阴性反应表明,TNF-α表达是由IORT引起的。IORT后> 30天,外膜中I型胶原蛋白沉积增加。在接受完整ERT疗程的两只动物中,观察到主要涉及平滑肌细胞的内膜增生。我们的研究结果表明,一些典型的放射性动脉硬化特征,如动脉周围纤维化和内膜增生,可早在照射后< 60天出现。巨噬细胞浸润以及血管中层平滑肌细胞中的TNF-α表达是自发性动脉粥样硬化病变发展的重要步骤。因此,高局部剂量X射线照射在动脉壁中早期诱导TNF-α可被视为慢性放射性动脉硬化的一个起始因素。