Objective:Radiotherapy, which is commonly used for the local control of thoracic cancers, also induces chronic inflammatory responses in the microvasculature of surrounding normal tissues such as the lung and heart that contribute to fatal radiation-induced lung diseases (RILDs) such as pneumonitis and fibrosis. In this study, we investigated the potential of cannabidiol (CBD) to attenuate the irradiation damage to the vasculature.Methods:We investigated the ability of CBD to protect a murine endothelial cell (EC) line (H5V) and primary lung ECs isolated from C57BL/6 mice from irradiation-induced damage in vitro and lung ECs (luECs) in vivo, by measuring the induction of oxidative stress, DNA damage, apoptosis (in vitro), and induction of inflammatory and pro-angiogenic markers (in vivo).Results:We demonstrated that a non-lethal dose of CBD reduces the irradiation-induced oxidative stress and early apoptosis of lung ECs by upregulating the expression of the cytoprotective mediator heme-oxygenase-1 (HO-1). The radiation-induced increased expression of inflammatory (ICAM-2, MCAM) and pro-angiogenic (VE-cadherin, Endoglin) markers was significantly reduced by a continuous daily treatment of C57BL/6 mice with CBD (i.p. 20 mg/kg body weight), 2 weeks before and 2 weeks after a partial irradiation of the lung (less than 20% of the lung volume) with 16 Gy.Conclusions:CBD has the potential to improve the clinical outcome of radiotherapy by reducing toxic side effects on the microvasculature of the lung.
目的：放射治疗常用于胸部肿瘤的局部控制，但其同时会诱发周围正常组织（如肺和心脏）微血管系统的慢性炎症反应，进而导致放射性肺炎及肺纤维化等致命性放射性肺损伤。本研究旨在探讨大麻二酚对减轻放射所致血管损伤的潜在作用。 方法：通过检测氧化应激、DNA损伤、细胞凋亡（体外）以及炎症与促血管生成标志物（体内）的诱导表达，评估CBD对小鼠内皮细胞系（H5V）、C57BL/6小鼠原代肺内皮细胞（体外）及活体肺内皮细胞（体内）的辐射防护作用。 结果：研究发现，亚致死剂量的CBD可通过上调细胞保护介质血红素加氧酶-1的表达，减轻放射诱导的肺内皮细胞氧化应激与早期凋亡。在C57BL/6小鼠肺局部（小于20%肺体积）接受16 Gy照射前2周至照射后2周期间，每日持续腹腔注射CBD（20 mg/kg体重），可显著降低放射诱导的炎症标志物（ICAM-2、MCAM）与促血管生成标志物（VE-钙黏蛋白、内皮糖蛋白）的表达升高。 结论：CBD具有通过减轻肺部微血管系统毒性副作用来改善放射治疗临床效果的潜力。
肿瘤(癌症)患者之家