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目的探讨应用携带血管细胞黏附分子-1(VCAM-1)分子探针的超声分子成像,评价下肢缺血“晚时间窗”炎症反应的可行性。方法 12只实验小鼠结扎一侧下肢股动脉制备缺血模型,另一侧股动脉为对照。术后第3天随机先后(间隔30 min)经尾静脉注入携抗小鼠VCAM-1单抗的靶向微泡(MB_V)和携同型抗体的对照微泡(MB_C),并于8 min后行对比超声检查,测量双侧下肢的显影强度(VI);最后进行双下肢病理学检查。结果对比超声图像显示:缺血下肢MB_V组可见明显的超声显影,VI值高达(18.4±2.9)U;而在缺血下肢MB_C组仅见轻度的超声显影,VI值为(6.9±1.2)U,两微泡组间比较差异有统计学意义(P<0.05)。两组微泡在非缺血下肢的VI值未见明显差异(P>0.05)。但无论MB_V还是MBC微泡,其在缺血下肢的VI值均明显高于非缺血下肢相应的VI值。免疫组化显示:缺血下肢血管有大量的VCAM-1表达,而非缺血下肢未见VCAM-1表达。结论应用VCAM-1分子探针的超声分子成像可有效评价下肢缺血“晚时间窗”的炎症反应。
Objective To investigate the feasibility of using molecular imaging of vascular endothelial cell adhesion molecule-1 (VCAM-1) molecular probe to evaluate the “late window” inflammatory reaction of lower limb ischemia. Methods Twelve experimental mice were sacrificed by ligating one femoral artery of the lower extremity to prepare an ischemic model. The other femoral artery was used as a control. On the 3rd day after operation, the targeted microbubbles (MB_V) and the control microbubbles (MB_C) carrying the anti-mouse VCAM-1 mAb were injected into the caudal vein at random intervals (30 min intervals) Contrast contrast ultrasonography was performed to measure the developing intensity of both lower extremities (VI). Finally, the pathology of both lower limbs was examined. Results Compared with ultrasound images, there was obvious ultrasonic imaging in the ischemic lower limbs MB_V group, the value of VI was as high as (18.4 ± 2.9) U; while in the ischemic lower limb MB_C group, only mild ultrasound imaging was found, the value of VI was (6.9 ± 1.2) U There was significant difference between the two microbubbles groups (P <0.05). There was no significant difference between the two groups in the non-ischemic lower limbs VI value (P> 0.05). But whether MB_V or MBC microbubbles, the VI value of ischemic lower limbs were significantly higher than the non-ischemic lower limb corresponding VI value. Immunohistochemistry showed that there was a large amount of VCAM-1 expression in ischemic lower extremity blood vessels, while no expression of VCAM-1 in non-ischemic lower limbs. Conclusion Ultrasound molecular imaging with VCAM-1 molecular probe can effectively evaluate the inflammatory reaction of lower limb ischemia and late-night window.