瑞典卡罗林斯卡医学院近日宣布,他们研究发现,癌症患者在接受放射性治疗后,动脉组织的基因表达发生变化,进而引发慢性炎症,使这些患者容易患心血管疾病。
卡罗林斯卡医学院在一份新闻公报中说,医学研究已证明,放射性治疗会增加患者患心血管疾病的风险,如乳腺癌患者接受放疗后容易发生心肌梗死,头颈肿瘤患者接受放疗后易中风等,但医生一直不清楚这些副作用产生的原因。
研究人员利用患者组织自体移植后,通过对受损组织和健康组织基因对比分析,研究了放射性治疗对人体血管产生的长期影响。这里所说的自体移植包括将患者的皮肤和肌肉等组织从身体的一部分移植到另一部分,以帮助修复因肿瘤切除而受损的组织,这些受损部位已接受过放疗。
研究人员在报告中介绍说,他们通过对同一患者同一时间颈动脉中经过和未经过放疗的组织的基因表达进行对比分析发现,接受过放疗的动脉组织基因的表达发生变化,进而引发慢性炎症,使这些患者容易患心血管疾病。
研究人员希望未来在这一研究的基础上,开发出能降低放疗副作用的新药。该研究成果已发表在最新一期《美国心脏病学会杂志》(JACC)上。
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《美国心脏病学会杂志》发表论文摘要(英文)
J Am Coll Cardiol, 2010; 55:1227-1236, doi:10.1016/j.jacc.2009.10.047
CLINICAL RESEARCH: RADIATION INJURY
Sustained Inflammation Due to Nuclear Factor-Kappa B Activation in Irradiated Human Arteries
Martin Halle, MD, PhD*,,*, Anders Gabrielsen, MD, PhD,, Gabrielle Paulsson-Berne, PhD, Caroline Gahm, MD, PhD, Hanna E. Agardh, BA, Filip Farnebo, MD, PhD* and Per Tornvall, MD, PhD,
Objectives: The aim of this study was to investigate gene expression networks related to cardiovascular disease in radiated human arteries.
Background: Recent epidemiological studies have shown that radiotherapy is associated with cardiovascular disease years after treatment. However, the molecular mechanisms underlying late effects of radiation are poorly described.
Methods: Arterial biopsies from radiated and nonradiated human conduit arteries, from the same patient, were simultaneously harvested during microvascular free tissue transfer for cancer-reconstruction in 13 patients, 4 to 500 weeks from radiation treatment. Radiated and nonradiated arteries were compared, with Affymetrix (Santa Clara, California) microarrays on a subset of the material to generate candidate genes. A Taqman (Applied Biosystems, Foster City, California) low-density array of 45 selected genes was designed for analysis of the whole material.
Results: Thirteen genes were synchronously expressed in all patients (p = 0.0015), including CCL8, CCL3, CXCL2, DUSP5, FGFR2, HMOX1, HOXA9, IL-6, MMP-1, PTX3, RDH10, SOD2, and TNFAIP3. A majority of differentially regulated genes related to the nuclear factor-kappa B (NF-B) signaling pathway and were dysregulated even years after radiation. The NF-B activation was confirmed by immunohistochemistry and immunofluorescence.
Conclusions: In the present study, we found sustained inflammation due to NF-B activation in human radiated arteries. The results are supported by previous in vitro findings suggesting that deoxyribonucleic acid injury, after radiation, activates NF-B. We also suggest that HOXA9 might be involved in the regulation of NF-B activation. The observed sustained inflammatory response can explain cardiovascular disease years after radiation.
Key Words: gene expression " human arteries " inflammation " irradiation