Stansby G, Chan Y C, Berwanger C S, Shurey S, Rook G A W, Stanford J L
Academic Surgical Unit, Imperial College School of Medicine at St. Mary's, London, UK.
Eur J Vasc Endovasc Surg. 2002 Jan;23(1):23-8. doi: 10.1053/ejvs.2001.1549.
we have tested the hypothesis that treatment with a mycobacterial preparation that modulates the antibody response, would diminish restenosis in a rat angioplasty model.
MATERIALS/METHODS: male Sprague-Dawley rats were used. All immunisations were given subcutaneously. Group A (control) received normal saline on days 0, 21, and 42. Group B received SRL172 on days 0, 21, and 42. Group C received SRL172 on days 0, 21, and 42, and hsp65/Incomplete Freund's on days 21 and 42. Group D received hsp65/Freund's on days 21 and 42. Right common carotid arteries were balloon-injured on day 63 using a standard technique known to produce MIH and animals were sacrificed on day 77. For each carotid 6 microm cross sections were cut from paraffin blocks. Cross-sectional areas were measured by computerised planimetry.
balloon injury resulted in MIH in all animals. Data represents mean+/-SEM for the percentage of area enclosed within the internal elastic lamina occupied by MIH (% MIH); which for groups A, B, C, and D was 85+/-11, 24+/-3, 27+/-7, and 17+/-3 respectively. All the treatment groups had significantly less MIH when compared to the control group but no statistically significant difference was found between any of the treatment groups.
this is the first report that immunomodulation with mycobacterial material suitable for use in man, can reduce MIH. Since such modulation has low risk, this raises the prospect of an important new therapeutic modality to combat restenosis.
我们已经验证了这样一个假设,即使用一种能调节抗体反应的分枝杆菌制剂进行治疗,会减少大鼠血管成形术模型中的再狭窄。
材料/方法:使用雄性斯普拉格-道利大鼠。所有免疫接种均皮下注射。A组(对照组)在第0、21和42天接受生理盐水。B组在第0、21和42天接受SRL172。C组在第0、21和42天接受SRL172,并在第21和42天接受hsp65/不完全弗氏佐剂。D组在第21和42天接受hsp65/弗氏佐剂。在第63天,使用一种已知会导致内膜增生的标准技术对右颈总动脉进行球囊损伤,并在第77天处死动物。从石蜡块上切下每个颈动脉的6微米横截面。通过计算机图像分析测量横截面积。
球囊损伤导致所有动物出现内膜增生。数据表示为内膜增生所占据的内弹性膜内面积百分比(%内膜增生)的平均值±标准误;A组、B组、C组和D组的该值分别为85±11、24±3、27±7和17±3。与对照组相比,所有治疗组的内膜增生均显著减少,但各治疗组之间未发现统计学上的显著差异。
这是第一份报告表明,用适合人类使用的分枝杆菌材料进行免疫调节可减少内膜增生。由于这种调节风险较低,这为对抗再狭窄带来了一种重要新治疗方式的前景。