中华皮肤科杂志 ›› 2014, Vol. 47 ›› Issue (11): 820-823.

• 研究报道 • 上一篇    下一篇

普萘洛尔治疗增殖期血管瘤的疗效及治疗前后血管内皮生长因子A和缺氧诱导因子1α的表达

凌彬1,尹小朋1,刘洁1,张静2,龚忠诚1,林兆全3   

  1. 1. 新疆医科大学第一附属医院
    2. 乌鲁木齐 新疆医科大学第一附属医院颌面肿瘤外科
    3. 新疆医科大学第一附属医院口腔颌面外科
  • 收稿日期:2014-01-16 修回日期:2014-08-18 出版日期:2014-11-15 发布日期:2014-11-01
  • 通讯作者: 林兆全 E-mail:LZQxhj@163.com
  • 基金资助:
    新疆维吾尔自治区自然科学基金面上项目：普萘洛尔对婴幼儿血管瘤抑制作用的初步研究。

Propranolol for proliferating hemangioma: therapeutic efficacy and expressions of vascular endothelial growth factor-A and hypoxia-inducible factor 1α in patients before and after treatment

  • Received:2014-01-16 Revised:2014-08-18 Online:2014-11-15 Published:2014-11-01

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摘要： 目的 分析普萘洛尔治疗增殖期婴幼儿血管瘤的临床疗效，并检测治疗过程中血清及尿液中血管内皮生长因子A（VEGF-A）和缺氧诱导因子1α（HIF-1α）的表达水平。 方法 增殖期婴幼儿血管瘤30例，口服普萘洛尔治疗，剂量为0.5 ~ 2 mg·kg-1·d-1。治疗前、治疗4周后、12周后分别测量瘤体半径，采用四级评估法及患者父母反馈进行临床疗效评估，酶联免疫吸附试验检测血清及尿液中VEGF-A和HIF-1α水平。健康对照组为儿保科正常体检婴幼儿30例。组间比较采用两因素方差分析，两两比较采用LSD法。 结果 患者组治疗12周后，2例疗效为优，11例好，14例中等，3例差。健康对照组血清VEGF-A水平为（268.174 ± 95.056） μg/L，HIF-1α水平为（10.809 ± 1.686） mg/L。患者组治疗前血清VEGF-A水平为（385.692 ± 136.146） μg/L，服药4周后为（264.853 ± 122.12） μg/L，12周后为（211.345±104.035） μg/L，呈逐渐下降趋势；血清HIF-1α水平分别为（31.462 ± 7.458）、（21.454 ± 5.489）和（12.052 ± 3.623） mg/L，亦呈逐渐下降趋势。患者组尿液中VEGF-A与HIF-1α的表达趋势与血清一致。患者组血清中VEGF-A与HIF-1α和尿液中VEGF-A与HIF-1α均呈正相关（r = 0.730，P < 0.05；r = 0.667，P < 0.05）；血清VEGF-A、尿液VEGF-A、血清HIF-1α以及尿液HIF-1α均与给药时程呈负相关（r值分别为－0.390、－0.689、－0.806、－0.683，P值分别 < 0.05、0.01、0.05、0.01）。 结论 普萘洛尔治疗增殖期婴幼儿血管瘤有效可能与降低外周血清和尿液中VEGF-A和HIF-1α水平有关。

关键词: 普萘洛尔, 血管瘤, 血管内皮生长因子A, 缺氧诱导因子1α

Abstract: Ling Bin, Yin Xiaopeng, Liu Jie, Zhang Jing, Gong Zhongcheng, Lin Zhaoquan. Oncology Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Xinjiang Medical University; Stomatology College of Xinjiang Medical University; Stomatology Research Institute of Xinjiang Uygur Autonomous Region, Urumqi 830054, China Corresponding author: Lin Zhaoquan, Email: lzqxhj@163.com 【Abstract】 Objective To evaluate the clinical efficacy of propranolol in treating proliferating infantile haemangiomas, and to measure the expression levels of vascular endothelial growth factor-A （VEGF-A） and hypoxia-inducible factor 1α（HIF-1α） in sera and urine of patients during the treatment. Methods Thirty infants with proliferating haemangiomas were treated with propranolol at doses of 0.5 － 2 mg/kg per day. The radius of haemangiomas was measured, and blood and urine samples were obtained from these patients before, and at 4 and 12 weeks after the beginning of treatment. Clinical efficacy was estimated according to a four-graded scale as well as the feedback from parents of these patients. Enzyme-linked immunosorbent assay （ELISA） was performed to determine the serum and urine concentrations of VEGF-A and HIF-1α. Thirty check-up infants collected from the Department of Child Health Care served as the healthy controls. Statistical analysis was done by two-way analysis of variance followed by the least significant difference （LSD） test. Results After 12 weeks of treatment, clinical response was excellent in 2 patients, good in 11, moderate in 14, and poor in 3. The serum levels of VEGF-A and HIF-1α were （268.174 ± 95.056） μg/L and （10.809 ± 1.686） mg/L respectively in the control group, sequentially decreased in the patients from baseline to 4 and 12 weeks after the beginning of treatment （VEGF-A: （385.692 ± 136.146） vs. （264.853 ± 122.12） vs. （211.345 ± 104.035） μg/L; HIF-1α: （31.462 ± 7.458） vs. （21.454 ± 5.489） vs. （12.052 ± 3.623） mg/L）. The trend in expression changes of VEGF-A and HIF-1α in urine samples was similar to that in blood samples in these patients. Positive correlation was observed between the expression level of VEGF-A and HIF-1α in sera （r = 0.730, P < 0.05） and urine （r = 0.667, P < 0.05） of these patients. Moreover, the levels of serum VEGF-A, urine VEGF-A, serum HIF-1α and urine HIF-1α were all negatively correlated with the time course following propranolol administration （r = －0.390, －0.689, －0.806, －0.683, P < 0.05, 0.01, 0.05, 0.01 respectively）. Conclusion Propranolol is effective for the treatment of proliferating infantile haemangiomas, likely by reducing serum and urinary concentrations of VEGF-A and HIF-1α in children.

Key words: Propranolol, Hemangioma, Vascular endothelial growth factor A, Hypoxia-inducible factor 1α