Mata Karina M, Tefé-Silva Cristiane, Floriano Elaine M, Fernandes Cleverson R, Rizzi Elen, Gerlach Raquel F, Mazzuca Marc Q, Ramos Simone G
Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Cardiovasc Pathol. 2015 Mar-Apr;24(2):110-20. doi: 10.1016/j.carpath.2014.10.004. Epub 2014 Nov 5.
Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation and degradation of the extracellular matrix, mediated by matrix metalloproteinases (MMPs). Doxycycline has been reported to control the progression of AAA by regulation of MMP. We hypothesized that doxycycline pretreatment in a rat model of AAA would cause reduction in gelatinolytic activity of MMP-2 and -9 and the inflammatory response in the wall of an aneurysm, consequently decreasing the formation and development of AAAs.
Male Wistar rats were divided into the following four groups: aneurysm (A); control (C); aneurysm+doxycycline (A+D) and control+doxycycline (C+D), with 24 animals per group subdivided into n=6 animals at different time points [1, 3, 7, and 15 days postsurgery (dps)]. The (A) and (A+D) groups simultaneously received the injury and extrinsic stenosis of the aortic wall. The (C) and (C+D) groups received sham operation. The treated animals received doxycycline via gavage (30 mg/kg/day) from 48 h before surgery until the end of experiment. At 1, 3, 7, and 15 dps, the animals were euthanized, and the aortas were collected for morphological analyses, immunohistochemistry, and zymography.
The animals from the (A) group developed AAAs. However, the animals treated with doxycycline showed a 85% decrease in AAA development, which was associated with a large reduction in gelatinolytic activity of MMP-2 and -9, and decreased inflammatory response (P<.05).
These results suggest that pretreatment with doxycycline before surgery inhibited the activity of MMP-2 and -9, as well as the inflammatory response, and may play an important role in the prevention of the development of AAAs.
腹主动脉瘤（AAA）的特征是细胞外基质的慢性炎症和降解，由基质金属蛋白酶（MMPs）介导。据报道，强力霉素可通过调节MMP来控制AAA的进展。我们假设在AAA大鼠模型中进行强力霉素预处理会导致MMP-2和-9的明胶酶活性降低以及动脉瘤壁的炎症反应，从而减少AAA的形成和发展。
雄性Wistar大鼠分为以下四组：动脉瘤组（A）；对照组（C）；动脉瘤+强力霉素组（A+D）和对照组+强力霉素组（C+D），每组24只动物，在不同时间点[术后1、3、7和15天（dps）]再细分为n = 6只动物。（A）组和（A+D）组同时接受主动脉壁损伤和外部狭窄。（C）组和（C+D）组接受假手术。处理后的动物从手术前48小时开始通过灌胃给予强力霉素（30 mg/kg/天），直至实验结束。在1、3、7和15 dps时，对动物实施安乐死，并收集主动脉进行形态学分析、免疫组织化学和酶谱分析。
（A）组的动物形成了AAA。然而，用强力霉素治疗的动物AAA发生率降低了85%，这与MMP-2和-9的明胶酶活性大幅降低以及炎症反应减弱有关（P<0.05）。
这些结果表明，术前用强力霉素预处理可抑制MMP-2和-9的活性以及炎症反应，可能在预防AAA的发展中起重要作用。
