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先天性心血管畸形的肺血管重构：一个历久弥新的话题
Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic
左向右分流型先天性心脏病最严重的并发症是肺动脉高压，肺动脉高压的实质是肺血管重构，因此，预防和逆转肺血管重构是提高患儿生存和生活质量的重要环节之一。本文从学科交叉的角度综述了肿瘤学和肿瘤药学领域的进展对肺血管重构衍化出的新研究视点，包括：从肿瘤学的DNA损伤应答机制调控研究中提炼出来的全新的 “ATM通路表达的折点假说”，提出了肺血管重构的关键环节——肺血管平滑肌细胞增殖的类肿瘤化可能是导致梗阻性肺动脉高压发生的基础病理；从肿瘤药学的化疗药物在较低的非细胞毒浓度下具有较强的抗血管生成特性的理论拓展出的肺靶向给药系统逆转肺血管重构研究。这些新的研究方向将为肺血管重构的治疗拓宽新的研究领域。
Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.
左向右分流先天性心脏病 / 肺血管重构 / DNA损伤应答 / 肺靶向给药
Left-to-right congenital heart disease / Pulmonary remodeling / DNA damage response / Lung-targeted drug delivery system
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