Gavish Lilach, Beeri Ronen, Gilon Dan, Rubinstein Chen, Berlatzky Yacov, Bulut Atilla, Reissman Petachia, Gavish Leah Y, Gertz S David
Institute for Medical Research-IMRIC, Hebrew University of Jerusalem, Jerusalem, Israel.
Lasers Surg Med. 2014 Dec;46(10):781-90. doi: 10.1002/lsm.22306. Epub 2014 Nov 19.
Using non-invasive, high-frequency ultrasonography (HF-u/s), we showed that low-level laser phototherapy (LLL) inhibits de-novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein-E-deficient (Apo-E(-/-)) mice. The current study tests the effect of LLL on the progression of pre-induced AAA.
STUDY DESIGN/MATERIAL AND METHODS: AAA was induced in Apo-E(-/-) mice (age 16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 0.01 mm resolution, Vevo-770, VisualSonics) was used to measure the maximum cross-sectional-diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm(2), 9 minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology.
Of all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non-treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P < 0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2-4 weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.24 ± 0.25 vs. -0.06 ± 0.39 mm, P = 0.029 by unpaired t-test). Similar results were obtained when limiting the analysis to animals with ≥ 50% expansion at 2 weeks. The deterioration in AWD from 2-4 weeks in non-treated controls was not observed in LLL-treated animals (ΔAWD: control, 0.03 ± 0.05 mm, P < 0.036 vs. LLL, 0.00 ± 0.05, P = 0.91 by paired t-test). By the modified Daugherty classification, we found significantly fewer severe aneurysms at 4 weeks in the LLL-treated animals versus control (3 of 10 vs. 9 of 11, P = 0.03 by FET).
LLL not only prevents de novo development of AAA, but, from this study, also arrests further progression of pre-induced AAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo-E(-/-) mice.
我们通过非侵入性高频超声检查（HF-u/s）发现，低强度激光疗法（LLL）可抑制载脂蛋白E缺陷（Apo-E(-/-)）小鼠腹主动脉瘤（AAA）的新生。本研究旨在测试LLL对预先诱导形成的AAA进展的影响。
研究设计/材料与方法：使用渗透微型泵（1000 ng/kg/分钟，持续4周）经皮下输注血管紧张素-II，在16 - 20周龄的Apo-E(-/-)小鼠中诱导AAA形成。使用HF-u/s（40 MHz，分辨率0.01 mm，VisualSonics Vevo-770）测量肾上腺上方腹主动脉的最大横截面直径（MCD）、前壁位移（AWD）和径向壁速度（RWV）。对在2周时MCD扩张超过基线35%的小鼠，经腹膜后暴露其主动脉，分别给予LLL治疗（780 nm，2.2 J/cm²，9分钟）或假手术处理。在4周时重复进行HF-u/s检查，通过灌注固定处死小鼠，切除主动脉进行组织病理学检查。
在2周时肾上腺主动脉MCD扩张超过35%的所有小鼠中，12只未治疗的小鼠中有7只（58%）在4周时MCD增加（>1个标准差），而14只接受LLL治疗的小鼠中只有1只（7%）出现这种情况（Fisher精确检验[FET]，P < 0.009）。LLL治疗组小鼠在2 - 4周时MCD的平均变化也显著降低（对照组与LLL治疗组，0.24 ± 0.25 vs. -0.06 ± 0.39 mm，非配对t检验，P = 0.029）。当将分析限制在2周时扩张≥50%的动物时，也得到了类似结果。在2 - 4周期间，未治疗的对照组中AWD恶化，而LLL治疗组未观察到这种情况（AWD变化：对照组，0.03 ± 0.05 mm，与LLL治疗组相比，P < 0.036；LLL治疗组，0.00 ± 0.05，配对t检验，P = 0.91）。根据改良的Daugherty分类法，我们发现LLL治疗组在4周时严重动脉瘤的数量明显少于对照组（10只中有3只 vs. 11只中有9只，FET，P = 0.03）。
LLL不仅可预防AAA的新生，而且从本研究来看，还能阻止预先诱导形成的AAA的进一步进展及其在Apo-E(-/-)小鼠主动脉壁生物力学完整性方面的相关恶化。
