Ricci M A, Strindberg G, Slaiby J M, Guibord R, Bergersen L J, Nichols P, Hendley E D, Pilcher D B
Department of Surgery, The University of Vermont College of Medicine, Burlington, Vermont, USA.
J Vasc Surg. 1996 Feb;23(2):301-7. doi: 10.1016/s0741-5214(96)70274-4.
Inflammation has been implicated as a contributing factor in the expansion of abdominal aortic aneurysms (AAA). To test this hypothesis, we examined the effects of a monoclonal antibody (MAB) to the leukocyte CD18 adhesion molecule on the expansion of experimental AAA.
Aneurysms were induced by perfusion of an isolated segment of the infrarenal aorta with elastase in 22 normotensive (WKY) and 17 genetically hypertensive (WKHT) rats. Animals of both strains were randomly allocated to control or MAB-treated groups (MAB, 5 microgram/100 gm body weight intraperitoneally, daily, beginning on the operative day for a total of four doses). The activity of the MAB against rat leukocytes had first been determined by in vitro immunofluorescence flow cytometry. Aortic size was directly measured initially and on day 14. At that time, a segment of aorta was stained with hematoxylin and eosin and mononuclear leukocytes and neutrophils were counted in each of 10 microscopic fields (400X).
The initial aortic size in all animals was 1.11+/-0.15 mm. All groups developed aneurysms significantly larger than the initial aortic size (p<0.01). However, the MAB-treated animals had significantly smaller aneurysms than the untreated controls (mm): WKY: 3.63+/-1.26, WKY-MAB: 2.08+/-0.30, WKHT: 4.54+/-1.86, WKHT-MAB: 2.37+/-0.40, p<0.0001. There also were significantly fewer monocytes in the MAB-treated normotensive rats: WKY:35.5+/-29.9, WKHT:40.6+/-28.8, WKY-MAB: 8.9+/-8.5, WKHT-MAB: 32.3+/-25.7, p=0.03. Neutrophil counts did not differ significantly between the groups.
Treatment with anti-CD18 monoclonal antibody slows the expansion of AAA in this experimental model. The associated inflammatory process at day 14, as indicated by monocyte infiltration, is reduced, but this effect may be opposed by the presence of hypertension. Further evaluation of the role of leukocytes and adhesion molecules in the expansion of AAA is warranted.
炎症被认为是腹主动脉瘤（AAA）扩张的一个促成因素。为了验证这一假设，我们研究了一种针对白细胞CD18黏附分子的单克隆抗体（MAB）对实验性AAA扩张的影响。
在22只血压正常的（WKY）大鼠和17只遗传性高血压（WKHT）大鼠中，通过向肾下腹主动脉的一个分离节段灌注弹性蛋白酶来诱导动脉瘤形成。将两种品系的动物随机分为对照组或MAB治疗组（MAB，5微克/100克体重，腹腔注射，每天一次，从手术日开始，共注射四剂）。MAB对大鼠白细胞的活性首先通过体外免疫荧光流式细胞术测定。最初和第14天时直接测量主动脉大小。此时，取一段主动脉用苏木精和伊红染色，并在10个显微镜视野（400倍）中分别计数单核白细胞和中性粒细胞。
所有动物的初始主动脉大小为1.11±0.15毫米。所有组形成的动脉瘤均明显大于初始主动脉大小（p<0.01）。然而，接受MAB治疗的动物的动脉瘤明显小于未治疗的对照组（毫米）：WKY：3.63±1.26，WKY-MAB：2.08±0.30，WKHT：4.54±1.86，WKHT-MAB：2.37±0.40，p<0.0001。在接受MAB治疗的血压正常的大鼠中，单核细胞也明显较少：WKY：35.5±29.9，WKHT：40.6±28.8，WKY-MAB：8.9±8.5，WKHT-MAB：32.3±25.7，p = 0.03。各组之间中性粒细胞计数无显著差异。
在这个实验模型中，用抗CD18单克隆抗体治疗可减缓AAA的扩张。如单核细胞浸润所示，第14天时相关的炎症过程有所减轻，但这种作用可能会被高血压的存在所抵消。有必要进一步评估白细胞和黏附分子在AAA扩张中的作用。
