携带抗P-选择素单抗靶向微泡和对比超声评价肾缺血再灌注损伤

目的探讨携带抗小鼠P-选择素单抗的靶向超声微泡（MBp）和对比超声（CEU）评价肾缺血再灌注损伤的可行性。方法12只实验小鼠随机均分为2组：缺血再灌注（IR组）和假手术组（SH组）,应用＂亲和素-生物素＂桥连法构建MBp。所有小鼠分别随机（间隔30min）经静脉弹丸注射给予普通脂质微泡（MB）和MBp,10min后行肾CEU检查,测量肾显影的声强度（VI）,最后进行肾组织免疫组化检测。结果第一帧CEU图像显示MBp及MB在IR组缺血再灌注肾分别可见显著及轻度的超声显影,而两者在SH组假手术肾均无明显的超声显影。VI值在IR组MBp较IR组MB及SH组MBp均明显增大（P〈0.05）;而在IR组MB较SH组MB轻度增大（P〈0.05）。免疫组化检测显示缺血再灌注肾血管内皮P-选择素表达较假手术肾明显增加。结论应用MBp行CEU检查可有效评价小鼠肾缺血再灌注损伤,将可用于评价微血管炎症或相关的血管内皮反应。

Evaluation of renal tissue ischemia-reperfusion injury with microbubbles targeted to P-selectin and contrast ultrasound

Objective To approach the feasibility on evaluation of renal tissue ischemia-reperfusion injury in mouse with microbubbles targeted to P-selectin (MBp) and contrast-enhanced ultrasound. Methods Twelve experimental mice were randomized into ischemia-reperfusion group (group IR) and sham-operated group (group SH) to construct MBp via "avidin-biotin " bridging chemistry. All mice were performed using renal contrast-enhanced ultrasound imaging (CEU) with general lipid microbubbles (MB) and MBp. After 10 min of intravenous bolus injection of MB or MBp, which were made in random order with 30 min interval, renal video intensity (VI) was determined. Then the kidneys were harvested for examination of immunohistochemisty. Results A significant enhancement was observed in the fist CEU picture in kidneys of group IR-MBp and IR-MB, while there was no marked enhancement in the fist CEU picture in kidneys of group SH-MBp or group SH-MB. As compared to group IR-MB and group SH-MBp, significantly increase in VI was observed in group IR-MBp (P<0.05). There was slightly increase of VI in group IR-MB compare to group SH-MB (P<0.05). Immunohistochemistry showed that endothelial P-selectin expression in renal tissues undergoing IR was greater than in SH. Conclusion CEU with MBp can effectively evaluate the renal ischemia-reperfusion injury in mouse. Site-targeted microbubbles may be used to evaluate the microvascular inflammation and other endothelial responses with CEU.