外涂普萘洛尔凝胶对婴幼儿血管瘤裸鼠模型瘤体的影响

Effects of topical propranolol hydrochloride gel for treatment of infantile hemangioma in nude mice

目的 探讨普萘洛尔凝胶治疗裸鼠血管瘤的有效性及安全性.方法 BALB /c（nu/nu）裸鼠30只,通过简单随机化分组法分为实验组、对照组和正常组,每组10只,于实验组和对照组裸鼠皮下注射血管瘤内皮细胞建立血管瘤模型,以3％普萘洛尔凝胶外涂实验组注射部位及其周围约0.5 cm正常皮肤,以及正常组裸鼠皮肤,对照组等待观察.定期记录、观察瘤体的生长情况,记录涂药部位皮肤水肿、红斑评分情况.细胞注射45 d后,处死裸鼠,以高效液相色谱荧光检测法检测实验组和正常组裸鼠普萘洛尔血药浓度,HE染色及免疫组化鉴定对照组瘤体组织CD31、CD34抗原表达情况.组间差异比较采用x2检验,计量资料采用均数＆#177;标准差表示.采用配对样本资料的t检验分析普萘洛尔凝胶外涂后瘤体体积、血药浓度及裸鼠皮肤变化情况.结果 细胞注射45 d,对照组瘤体体积为（366.57＆#177;17.08） mm3,明显高于实验组的（13.36＆#177;2.09） mm3,2组比较差异有统计学意义（P＜0.05）;正常组血药浓度为（16.83＆#177;1.53） ng/ml,实验组为（18.42 ＆#177;2.21） ng/ml,2组比较差异无统计学意义（P＞0.05）.实验组与对照组皮肤刺激分值均为0分.结论 局部外涂普萘洛尔凝胶可以抑制裸鼠血管瘤瘤体的生长,皮肤刺激性小,可以长期安全使用.

Objective To explore the effect and safety of topical propranolol hydrochloride gel for treatment of infantile hemangioma.Mehods Thirty nude mice（BALA/c, nu/nu）were divided into three groups, experimental group, control group and normal group.Human hemangioma endothelial cells cultured in vitro were injected subcutaneously in experimental group and control group to establish infantile hemangioma model.Topical propranolol hydrochloride gel was applied on the surface of the hemangioman in experimental group and normal group.Tumor volumn change and the skin situations （edema, erythema, ulceration） were observed at different periods.45 days after cell injection, the mice were killed and plasma concentration was detected in the experimental group and the control group by high performance liquid chromatography with evaporative light scattering detector, and tumors were subjected to histopathologic examination and immunohistochemistry for CD31 and CD34.The correlation between volumes and plasma concentration was statistically analyzed with SPSS 13.0 paired samples t test with α =0.05 as statistical standard.Results At 45 days, the volume of the tumor in control group was （366.57 ± 17.08） mm3 ,which has a significant difference as compared to the experimental group（13.36 ± 2.09） mm3（P 〈 0.05）;and the plasma concentration was （16.83 ± 1.53） ng/ml in experimental group, and （18.42 ± 2.21） ng/ ml in normal group （P 〉 0.05）.Topical propranolol hydrochloride gel （3%） has no irritation to nude mice＇s skin.Conclusions Topical application of 3% propranolol hydrochloride gel is effective and safe for the treatment of infantile hemangioma.