Fu Y, Yang Z-G, Zhao L-Y
Department of Burns and Plastic Surgery, Binzhou Medical University Hospital, Binzhou, China. zhaolianying201605@163.
Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1276-1280.
To study pathogenic features of pediatric hemangiomas, we successfully established a model in mice, by transplanting human hemangioma tissues.
The hemangioma from the leg of a two-month-old infant was dissected and sliced into several pieces. During a careful surgical procedure, the hemangioma tissues were individually transplanted into skin incisions in anesthetized mice. The volume of the transplanted tumors was measured and the changes in shape recorded at 1 day, and at 1, 2, 3, 4, 5 and 6 months after the transplantation. HE dyeing, CD31 and Glut1 IHC were applied to tumors in the proliferation and involuting phases. Also, 10 survival tumors and 10 normal tissues from infants undergoing circumcisions (control tissues) were used to determine their Angiotensin 1 (Ang1), Angiotensin 2 (Ang2), Tie2, and endothelium growth factor (VEGF) expression levels by IHC method.
We observed all the tumors going through the same stages, where after two months their volumes increased sharply and then after 4 months they all began to recede. During the proliferative phase, newly born capillaries could be seen and the tumor elasticity increased (bright red color). During the involuting phase, the color faded away and the tumors became harder and were almost gone by 6 months. During the first two months after transplantation, HE dyeing showed hypertrophied and proliferating endothelial cells accumulating inside the tumors with irregular cavities inside blood vessels being filled by them. During the involuting phase (at 4 months), the lumen in blood vessels was distinctly enlarged while fiber and adipose tissue had significantly deposited. The transplanted and original tumors tested positive for CD31 and Glut1 dyeing, without significant differences. Compared with control samples, the Ang1 expression of the transplanted tumor in both the hyperplasia and proliferative phases was stably low (p<0.05), while expressions of Ang2 and Tie2 were both stably high (p<0.05). The VEGF expression in the tumors, however, was high during the proliferative phase (p<0.05), while the VEGF of the involuting phase showed no significant differences from that of the normal samples (p>0.05).
We showed the reliability of the mouse model in reflecting the pathologic evolution of the proliferation and involuting phases of infantile hemangiomas. Angiogenic mediators Ang1, Ang2 and Tie2 may be abnormally expressed and play important roles in the development of this angiogenic disease.
为研究小儿血管瘤的致病特征，我们通过移植人血管瘤组织成功建立了小鼠模型。
将一名两个月大婴儿腿部的血管瘤进行解剖并切成数块。在精细的手术过程中，将血管瘤组织分别移植到麻醉小鼠的皮肤切口处。测量移植瘤的体积，并记录移植后1天以及1、2、3、4、5和6个月时肿瘤形状的变化。对增殖期和消退期的肿瘤进行苏木精-伊红（HE）染色、CD31和葡萄糖转运蛋白1（Glut1）免疫组化检测。此外，选取10个存活的肿瘤以及10个接受包皮环切术婴儿的正常组织（对照组织），采用免疫组化方法检测其血管紧张素1（Ang1）、血管紧张素2（Ang2）、酪氨酸激酶受体2（Tie2）和血管内皮生长因子（VEGF）的表达水平。
我们观察到所有肿瘤经历相同阶段，两个月后体积急剧增大，4个月后均开始消退。在增殖期，可见新生毛细血管，肿瘤弹性增加（呈鲜红色）。在消退期，颜色变淡，肿瘤变硬，到6个月时几乎消失。移植后前两个月，HE染色显示肿瘤内肥大和增殖的内皮细胞聚集，血管内不规则腔隙被其填充。在消退期（4个月时），血管腔明显扩大，纤维和脂肪组织显著沉积。移植瘤和原发瘤CD31和Glut1染色均呈阳性，无显著差异。与对照样本相比，移植瘤在增生期和增殖期的Ang1表达均稳定较低（p<0.05），而Ang2和Tie2表达均稳定较高（p<0.05）。然而，肿瘤中VEGF表达在增殖期较高（p<0.05），而消退期的VEGF与正常样本无显著差异（p>0.05）。
我们证明了该小鼠模型在反映婴儿血管瘤增殖期和消退期病理演变方面的可靠性。血管生成介质Ang1、Ang2和Tie2可能异常表达，并在这种血管生成性疾病的发展中起重要作用。
