摘要
目的探讨高强度聚焦超声（HIFu）消融神经母细胞瘤SD（Sprague-Dawley）荷瘤幼鼠模型后对骨骼生长发育的影响。方法4周龄健康雄性SD幼鼠135只，随机分为A组正常对照组、B组HIFU组和C组手术组，每组45只。选择人神经母细胞瘤SK-N-SH细胞接种于HIFU组SD幼鼠左侧肾上腺区肾筋膜内，制作荷瘤鼠模型，接种后7～9d（肿瘤最大直径1．0～1．5cm）时接受HIFU治疗，功率70-90W，手术组仅接种SK—N-SH细胞，正常对照组不做任何处理。3组分别于HIFU前、HIFU后3d、2周和4周监测身长、肉眼及X线观察骨骼有无畸形出现，酶联免疫法（ELISA）检测血清骨碱性磷酸酶（BALP）浓度，组织病理切片行HE染色观察HIFU辐照区周围脊柱骨的骨小梁形态变化。结果治疗前、治疗后不同时期肉眼观察及X线检查3组SD幼鼠骨骼未发现明显畸形；治疗后3dSD荷瘤鼠身长增长值HIFU组（0．900±0．338）cm小于正常组（1．497±0．362）cm和手术组（1．243±0．378）cm（P〈0．05），治疗后2周结果显示HIFU组（2．500±0．445）em小于正常组（3．633±0．434）cm和手术组（3．333±0．372）cm（P〈0．05），正常组与手术组身长增长值差异不明显（P〉0．05）；治疗后4周HIFU组（2．533±0．543）cm、正常组（2．900±0．541）cm和手术组（2．633±0．696）CN身长增长值两两比较差异不明显（P〉0．05）；血清BALP治疗后3dHIFU组（951．697±251．618）pg／ml低于正常组（1168．847±121．638）pg／ml和手术组（1088．359±176．919）pg／ml（P〈0．05），治疗后2周HIFU组（1037．507±297．013）pg／ml低于正常组（1675．691±309．506）pg／ml和手术组（1915．433±212．364）pg／ml（P〈0．05），正常组与手术组差异不明显（P〉0．05）；血清BALP治疗后4周HIFU组（1106．551±235．832）pg／ml、正常组（1219．494±77．615）pg／ml和手术组（1092．835±164．593）pg／ml，3组差异不明显（P〉0．05）。HE染色光镜下观察HIFU组在治疗后3d、2周骨小梁变细，初级骨髓腔明显扩大，治疗后4周骨小梁及骨髓腔形态无明显差异。结论HIFU消融人神经母细胞瘤荷瘤SD幼鼠模型后，短时间内可抑制SD荷瘤鼠模型骨骼的生长发育，HIFU的抑制作用可能会随着青春期骨骼生长发育高峰期在成年期消失。
Objective To explore the effects of high intensity focused ultrasound （HIFU） abla- tion on skeletal growth in infant rats bearing human neuroblastoma. Methods A total of 135 healthy 4-week-old male Sprague-Dawley （SD） rats were divided randomly into normal control group （A）, HIFU group （B） and surgery group （C） （n = 45 each）. Human neuroblastoma SK-N-SH cells were inoculated into renal fascia of left adrenal gland for constructing a tumor-bearing rat model in HIFU and surgery groups. The rats of HIFU group received HIFU with a power of 70-90 W at Days 7-9 post-inoculation （tumor diameter 1.0-1.5 cm）. While those of normal control and surgery groups wereuntreated. The data of length, skeletal malformations under macroscopic observation and radiography were recorded at study entry and after 3 days, 2 weeks and 4 weeks in all groups. The serum level of bone alkaline phosphatase （BALP） was measured by enzyme-linked immunosorbent assay （ELISA） and histopathological examinations of spine and ribs around HIFU radiation zone were made with he- matoxylin ＆ eosin stain. Results No obvious macroscopic and radiographic malformations were found at study entry and different stages after HIFU. The height growth at day 3 in HIFU group [（0. 900 ± 0. 338） em] was significantly lower than that in control group [（1. 497 ± 0. 362） cm] and surgery group [（1. 243 ± 0. 378） cm] （P〈0. 05）. At week 2, it was also lower in HIFU group （2. 500 ± 0. 445） cm than control group （3. 633 ± 0. 434） em and surgery group [-（3. 333 ± 0. 372） cm] （P〈 0. 05）. However, no difference existed among HIFU group [（2. 533 ± 0. 543）cm], control group [（2. 900±0. 541） cm] and surgery group [（2. 633 ± 0. 696） cm] at Week 4（P〉0. 05）. The serum concentration of BALP decreased after HIFU treatment 3 days in HIFU group [（951. 697 ± 251. 618） pg/ml] than that in control group [（1 168. 847 ± 121. 638） pg/ml] and surgery group [（1 088. 359 ± 176. 919） pg/ml]（P〈0. 05）. Significant statistical differences existed when HIFU group [（1 037. 507 ± 297. 013） pg/ml] compared with control group [（1 675. 691 ± 309. 506） pg/ml] and surgery group F（1 915. 433 ± 212. 364） pg/ml] at 2 weeks later（P〈0. 05）. However, no statistical difference exis- ted in the serum concentration of BALP among HIFU group [（1 106. 551 ± 235. 832） pg/ml], control group [（1 219. 494 ± 77. 615） pg/ml] and surgery group [（1 092. 835 ± 164. 593） pg/ml] at Week 4（P 〉0. 05）. Histopathological examination showed that bone trabeculae narrowed, primary marrow cavi- ty significantly expanded at day 3 and week 2 post-HIFU in HIUF group. At week 4, bone trabecular density was similar in three groups. Conclusions HIFU may transiently inhibit skeletal growth in in- fant rats bearing human neuroblastoma. Such an effect shall disappear with a peak of adolescent bone growth and development.
出处
《中华小儿外科杂志》
CSCD
北大核心
2014年第2期109-114,共6页
Chinese Journal of Pediatric Surgery
关键词
神经母细胞瘤
高强度聚焦超声消融
骨骼
Neuroblastoma
High intensity focused ultrasound ablatiom Skeleton
