Ulinastatin Inhibits the Formation and Progression of Experimental Abdominal Aortic Aneurysms
Ulinastatin Inhibits the Formation and Progression of Experimental Abdominal Aortic Aneurysms
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乌司他丁抑制实验性腹主动脉瘤的形成和进展
DOI：
10.1159/000504848
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发表时间：
2020-03-01
影响因子：
1.7
通讯作者：
Yuan, Hai
中科院分区：
文献类型：
--
作者：
Li, Gang;Zhou, Hua;Yuan, Hai
目的：腹主动脉壁炎性损伤在腹主动脉瘤(AAA)发病中起重要作用。近年来，乌司他丁(UTI)因其抗炎作用而备受关注。本研究旨在评价尿路感染对实验性腹主动脉瘤的潜在影响。方法：经腹主动脉注入猪胰腺弹性酶(PPE)建立小鼠腹主动脉AAA模型。给小鼠灌胃UTI(50000 U/kg/d)。从注射PPE后即刻或第4天开始，一直持续到第14天。通过主动脉内径测量和主动脉组织病理学分析评价UTI的疗效。结果：对照组小鼠从第0天起持续存在显著的、随时间变化的主动脉内径增大。在UTI组，主动脉内径增加，主动脉壁平滑肌细胞和弹性蛋白的耗竭明显减轻。同时，UTI还能抑制CD68+巨噬细胞、CD8+T细胞和B220+B细胞密度以及新生血管生成。此外，延迟的UTI治疗仍然可以有效地限制动脉瘤的扩大。结论：UTI治疗可抑制实验性AAA的形成和生长，UTI可能是治疗早期AAA疾病的一种潜在的治疗方法。
Aims: Aortic mural inflammatory damage takes a vital part in abdominal aortic aneurysm (AAA). Recently, ulinastatin (UTI) has attracted attention for its anti-inflammatory function. Our study aimed to evaluate potential influences of UTI on experimental AAA. Methods: A mouse model of AAA was induced by infusion of porcine pancreatic elastase (PPE) into the abdominal aorta. Mice were treated with UTI (50,000 U/kg/day i.p.) beginning either immediately or on the 4th day after PPE infusion, with treatment being continued until the 14th day. UTI effects were assessed by aortic diameter measurements and aortic histopathological analysis. Results: Significant and time-dependent aortic diameter enlargement persisted in the control mice from day 0. In the UTI group, aortic diameter increased, and depletion of aortic mural smooth muscle cells and elastin was significantly attenuated. Simultaneously, mural CD68+ macrophages, CD8+ T-cell and B220+ B-cell density, as well as neoangiogenesis were suppressed by UTI. In addition, delayed UTI treatment could still effectively limit aneurysm expansion. Conclusions: UTI treatment limits the formation and growth of experimental AAA, and UTI may be a potential treatment for early AAA disease.