口服普萘洛尔对增殖期血管瘤患儿尿液bFGF、MMP-2和MMP-9表达水平的影响

目的: 探讨增殖期婴幼儿血管瘤患儿口服普萘洛尔前、后2个月尿液中bFGF、MMP-2和MMP-9的表达水平变化,初步探索普萘洛尔治疗婴幼儿血管瘤的作用机制。方法: 收集2018年6月—2019年6月在中国医科大学附属口腔医院口腔颌面外科病区住院的增殖期血管瘤患儿34例。分别在患儿口服普萘洛尔前、后2个月留取清晨无菌中段尿10 mL,另外收集21例正常婴幼儿（年龄<12个月）的清晨无菌中段尿10 mL作为对照组,采用酶联免疫吸附法检测3组尿液样本中bFGF的表达水平,采用明胶酶谱法检测3组尿液样本中MMP-2和MMP-9的表达水平。采用SPSS 22.0软件包对数据进行统计学分析。结果: 口服普萘洛尔后2个月,患儿尿液中bFGF的表达水平显著低于治疗前（P<0.01）,但仍显著高于对照组（P<0.05）;MMP-2和MMP-9的表达水平显著低于治疗前（P<0.01）,但仍高于对照组（P<0.05）。结论: 普萘洛尔治疗增殖期血管瘤患儿的作用机制之一,可能是通过抑制患儿体内bFGF、MMP-2和MMP-9的表达水平,进而抑制血管瘤中血管内皮细胞的增殖与血管生成,达到治疗血管瘤的目的。检测尿液中bFGF、MMP-2和MMP-9的表达水平,可作为患儿口服普萘洛尔用药过程中的评价指标。

Effects of oral propranolol on urine bFGF,MMP-2, MMP-9 expression in children with proliferative infantile hemangioma

PURPOSE: To investigate the effect of propranolol on urine bFGF, MMP-2, MMP-9 expression of children with proliferative infantile hemangioma(IH), so as to clarify the mechanism of propranolol in treating IH. METHODS: From June 2018 to June 2019, thirty-four children with proliferative IH were treated with oral propranolol. In addition, twenty-one normal children (age <12 months) were chosen as the control group. 10 mL of sterile morning urine were collected before and 2 months after oral administration of propranolol in infants with IH. All blood samples were placed in ordinary disinfection test tubes, centrifuged at 1 000 r/min for 10 min, the supernatant of urine was collected and stored separately. The urine samples of normal control group were processed in the same way. The expression levels of bFGF in the urine of children with proliferative IH before and 2 months after oral administration of propranolol and in the normal control group were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of MMP-2 and MMP-9 in the urine of children with proliferative IH before and 2 months after treatment and in the control group were detected by gelatin zymography. SPSS 22.0 software package was used to analyze the data. RESULTS: Two months after oral propranolol treatment, the concentration of bFGF in urine was significantly lower than that before treatment (P<0.01), but still significantly higher than that in the control group (P<0.05). The expression levels of MMP-2 and MMP-9 were significantly lower than those before treatment(P<0.01), but still higher than those in the control group (P<0.05). CONCLUSIONS: One of the mechanisms of propranolol in the treatment of children with proliferative IH may be through inhibiting the expression levels of bFGF, MMP-2 and MMP-9, and then inhibiting the proliferation and angiogenesis of vascular endothelial cells in IH, so as to achieve the effect of treating hemangioma. The detection of the expression levels of bFGF, MMP-2 and MMP-9 in urine can be used as the index for oral propranolol treatment of children with proliferative IH.