Statius van Eps R G, ChandraSekar N R, Hasan T, LaMuraglia G M
Division of Vascular Surgery of the General Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Photochem Photobiol. 1998 Mar;67(3):337-42.
Intimal hyperplasia (IH) plays a dominant role in the development of restenosis. In previous studies, photodynamic therapy (PDT) prevented IH induced by segmental balloon injury of the rat carotid. The critical elements required to control IH effectively with this technique are not fully understood. This study assessed the importance of the treatment field by studying the repair process of injured vessels, in which the PDT-treatment field did not target the entire injured area. The entire rat common carotid artery was balloon-injured to induce IH, whereas only the cervical segment below the bifurcation was subjected to PDT by external light irradiation after administration of the photosensitizer chloroaluminum sulfonated phthalocyanine. Light irradiation of injured arteries without photosensitizer served as control for PDT, and PDT of uninjured arteries was included as a control group for the balloon injury. Histologic characterization of the repair process was sequentially assessed. Balloon-injured arteries without PDT displayed rapid IH development with a peak at 2 weeks. Photodynamic therapy of balloon-injured arteries resulted in complete local depletion of medial smooth muscle cells (SMC), which was associated with a lack of IH until 2 weeks. However, at 4 and 16 weeks there was significant IH in PDT-treated arteries despite a lack of medial SMC repopulation. A wave of IH progression over the acellular media was observed in these arteries, migrating from the injured non-PDT-treated area. The PDT of uninjured arteries did not result in IH and was also associated with a persistent acellular media. Delayed IH development after PDT of injured vessels can result from IH progression from an injured site not included in the treatment field. This also indicated that the source of cells developing the intimal hyperplasia lesion can originate from an area remote from the lesion. Together with previous results and the determination that PDT itself does not induce IH, it can be reasoned that inclusion of the whole injured artery or a section of an uninjured margin in the treatment field is essential for effective PDT prevention of IH.
内膜增生（IH）在再狭窄的发生发展中起主导作用。在先前的研究中，光动力疗法（PDT）可预防大鼠颈动脉节段性球囊损伤诱导的内膜增生。用该技术有效控制内膜增生所需的关键因素尚未完全明确。本研究通过研究损伤血管的修复过程评估了治疗区域的重要性，其中PDT治疗区域并未覆盖整个损伤区域。将大鼠的整个颈总动脉进行球囊损伤以诱导内膜增生，而在给予光敏剂磺化铝酞菁后，仅通过外部光照射对分叉以下的颈段进行PDT治疗。对未给予光敏剂的损伤动脉进行光照射作为PDT的对照，对未损伤动脉进行PDT作为球囊损伤的对照组。对修复过程进行组织学特征的序贯评估。未进行PDT的球囊损伤动脉内膜增生迅速发展，在2周时达到峰值。对球囊损伤动脉进行光动力疗法导致中膜平滑肌细胞（SMC）完全局部耗竭，这与2周内无内膜增生相关。然而，在4周和16周时，尽管中膜SMC没有重新填充，但接受PDT治疗的动脉出现了明显的内膜增生。在这些动脉中观察到一波内膜增生在无细胞中膜上进展，从未接受PDT治疗的损伤区域迁移而来。对未损伤动脉进行PDT未导致内膜增生，且也与持续的无细胞中膜相关。损伤血管接受PDT治疗后内膜增生延迟发展可能是由于内膜增生从治疗区域未包括的损伤部位进展而来。这也表明形成内膜增生病变的细胞来源可源自远离病变的区域。结合先前的结果以及PDT本身不会诱导内膜增生的判定，可以推断在治疗区域纳入整个损伤动脉或一段未损伤边缘对于PDT有效预防内膜增生至关重要。
