外涂普萘洛尔凝胶对浅表型增殖期婴幼儿血管瘤患者血浆VEGF、bFGF和MMP-9的影响

Effect of propranolol gel on plasma VEGF, bFGF and MMP-9 in proliferating infantile hemangiomas of superficial type

目的 探讨普萘洛尔凝胶对浅表型增殖期婴幼儿血管瘤患儿（IHs）血浆血管内皮生长因子（VEGF）、碱性成纤维生长因子（bFGF）和基质金属蛋白酶-9（MMP-9）的影响.方法 选取2013年2月至2014年2月厦门大学附属东方医院普通外科,采用普萘洛尔凝胶治疗的33例浅表型增殖期婴幼儿血管瘤患儿的临床资料,采用Achauer分级标准评估疗效,ELISA检测治疗前和治疗后l、3个月时血浆VEGF、bFGF和MMP-9含量,并与30例健康婴幼儿进行对照.健康婴幼儿和治疗前婴幼儿血管瘤患儿2组间计量资料,采用Mann-Whitney U-test检验,婴幼儿血管瘤患儿治疗前及治疗后1、3个月,此3个时间点中任意2个时间点的比较,采用配对Wilcoxon符合秩检验,数据采用SPSS 13.0进行分析.结果 IHs治疗l、3个月后的有效率分别为45.45％和81.82％.患儿治疗前血浆VEGF和MMP-9含量分别为（362.16 ±27.29） pg/ml和（1 376.41±42.15） pg/ml,均高于健康婴幼儿的（85.63 ±8.14） pg/ml和（687.27 ±44.15） pg/ml,P＜0.05;bFGF在IHs和健康婴幼儿间无明显差异[（235.94±35.43） pg/ml和（176.03±13.60） pg/ml],P＞0.05.IHs治疗后1个月,VEGF和bFGF含量分别为（271.51 ±18.59） pg/ml和（135.85 ±12.66） pg/ml,较治疗前显著减少,P ＜0.05;治疗后3个月VEGF和bFGF含量分别为（240.80±19.89） pg/ml和（107.31±5.82）pg/ml,与治疗前比较,P＜0.05.治疗后l、3个月,MMP-9含量分别为（1 321.18±48.74） pg/ml和（1 468.68 ± 32.78） pg/ml,未见明显下降,P＞0.05.结论 普萘洛尔凝胶治疗浅表型增殖期婴幼儿血管瘤致血浆VEGF、bFGF含量减少,可能与其抑制婴幼儿血管瘤的增殖有关.

Objective To investigate the effect of topical propranolol gel on the levels of plasma vascular endothelial growth factor （VEGF）,basic fibroblastic growth factor （bFGF） and matrix metalloproteinases-9 （MMP-9） in proliferating infantile hemangiomas （IHs） of superficial type.Methods 33 consecutive children with superficial IHs were observed pre-treatment,1 and 3 months after application of topical propranolol gel for the levels of plasma VEGF,MMP-9 and bFGF by enzyme-linked immunosorbent assay （ELISA） in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014.The plasma results of IHs were compared with those of 30 healthy infants.The clinical efficacy in IHs was evaluated by Achauer system.Differences of plasma results between the healthy group and the IHs group pre-treatment were analyzed using Mann-Whitney U-test.Paired sample comparisons of any two time points of pre-treatment,1 month and 3 months after treatment in IHs were evaluated by Wilcoxon signed-rank test.Results The clinical efficiency of topical propranolol gel at 1,3 months after application were 45.45%,81.82% respectively.The levels of plasma VEGF and MMP-9 in patients pretreatment were higher than those in healthy infants [（362.16 ±27.29） pg/ml vs （85.63 ± 8.14） pg/ml,（1 376.41 ±42.15） pg/ml vs （687.27 ±44.1） pg/ml,P〈0.05],but the level ofbFGF did not show significant difference [（176.03 ± 13.60） pg/ml vs （235.94 ± 35.43） pg/ml,P 〉 0.05].The concentrations of VEGF and bFGF at 1,3 months after treatment decreased obviously [（271.51 ± 18.59） pg/ml vs （362.16 ±27.29） pg/ml,（135.85 ±12.66） pg/ml vs （176.03 ±13.60） pg/ml],1 month after treatment vs pre-treatment,P 〈 0.05; （240.80 ± 19.89） pg/ml vs （362.16 ± 27.29） pg/ml,（107.31 ±5.82） pg/ml vs （176.03 ± 13.60） pg/ml,3 month after treatment vs pre-treatment,P 〈 0.05,whereas the levels of plasma MMP-9 declined slightly [（1 321.18 ±48.74） pg/ml vs （1 376.41 ± 42.15） pg/ml,（1 468.68 ±32.78） pg/ml vs （1 376.41 ±42.15） pg/ml,P〉0.05].Conclusions Propranolol gel may suppress the proliferation of superficial infantile hemangiomas by reducing VEGF and hFGF.