Heckenkamp Joerg, Luebke Thomas, Theis Thorsten, Schumacher Lukas, Gawenda Michael, Thul Roland, Fries Jochen W U, Brunkwall Jan
Department of Vascular Surgery, University of Cologne, Cologne, Germany.
Interact Cardiovasc Thorac Surg. 2012 Jul;15(1):69-72. doi: 10.1093/icvts/ivs124. Epub 2012 Apr 3.
The hypothesis driving this study was that photodynamic therapy (PDT) may limit abdominal aortic aneurysm growth due to matrix changes. The aortas of 12 rats were incubated with elastase using a newly modified experimental aneurysm model (3.5 mg/ml). Rats were allocated to an elastase-only group (n = 6) to study the elastase-induced aneurysm growth and an elastase ± PDT group to evaluate if PDT limited aneurysm growth (n = 6). PDT was performed with the photosensitizer methylene blue, and thermoneutral laser light (660 nm) was applied (120 J/cm(2), 100 mW/cm(2)) using a diode laser. Four untreated rats served as controls. The arteries were analysed after 4 weeks based on histology, immunohistochemistry and morphometry. This modified rat elastase model led to reproducible aneurysm development with no elastase-induced mortality compared with control animals (circumference, controls: 2.9 ± 0.2 vs. elastase: 5.5 ± 0.9 mm; P < 0.01). PDT after elastase incubation did not inhibit inflammatory cell infiltration. No significant change in the circumference was observed between elastase incubation and PDT treatment after elastase incubation (circumference, elastase: 5.5 ± 0.9 vs. elastase and PDT: 6.1 ± 0.8 mm; P < 0.01). Despite a PDT-induced resistance to protease digestion, PDT did not reduce aortic dilatation in the elastase-treated rat aorta. These findings suggest that PDT may not be a useful modality to prevent aneurysm growth.
本研究的假设是光动力疗法(PDT)可能由于基质变化而限制腹主动脉瘤的生长。使用新改良的实验性动脉瘤模型(3.5mg/ml),将12只大鼠的主动脉与弹性蛋白酶一起孵育。将大鼠分为仅弹性蛋白酶组(n = 6)以研究弹性蛋白酶诱导的动脉瘤生长,以及弹性蛋白酶±PDT组以评估PDT是否限制动脉瘤生长(n = 6)。使用光敏剂亚甲蓝进行PDT,并使用二极管激光施加热中性激光(660nm)(120J/cm²,100mW/cm²)。4只未处理的大鼠作为对照。4周后基于组织学、免疫组织化学和形态计量学对动脉进行分析。与对照动物相比,这种改良的大鼠弹性蛋白酶模型导致可重复的动脉瘤形成,且无弹性蛋白酶诱导的死亡率(周长,对照组:2.9±0.2 vs.弹性蛋白酶组:5.5±0.9mm;P<0.01)。弹性蛋白酶孵育后进行的PDT并未抑制炎性细胞浸润。弹性蛋白酶孵育后与弹性蛋白酶孵育加PDT处理之间未观察到周长有显著变化(周长,弹性蛋白酶组:5.5±0.9 vs.弹性蛋白酶加PDT组:6.1±0.8mm;P<0.01)。尽管PDT诱导了对蛋白酶消化的抗性,但PDT并未减少弹性蛋白酶处理的大鼠主动脉的扩张。这些发现表明,PDT可能不是预防动脉瘤生长的有效方法。