BALB/c裸鼠血管瘤模型的建立及普萘洛尔对其瘤体的抑制作用

Establishment of BALB/c hemangioma model in nude mice and the inhibitory effect of propranolol on it

目的建立BALB/c裸鼠血管瘤模型,探讨普萘洛尔对血管瘤裸鼠移植瘤瘤体生长的影响。方法手术切除血管瘤患儿血管瘤组织,经皮肤切口移植于40只BALB/c裸鼠建立血管瘤模型。移植后第45天将40只荷瘤小鼠随机分为5组:治疗组1,腹腔注射0.01%普萘洛尔溶液0.4 mL;治疗组2,腹腔注射0.05%普萘洛尔溶液0.4 mL;治疗组3,腹腔注射0.1%普萘洛尔溶液0.4 mL;治疗组4,经口灌胃0.01%普萘洛尔溶液0.4 mL;对照组,腹腔注射无菌生理盐水0.4 mL;各组给药均为1次/d,持续1周。于干预前及干预后第7、14、21天测量各组瘤体体积和小鼠体质量并进行比较;干预第22天切取瘤体行HE染色观察对比病理变化。结果干预后第7、14、21天,治疗组1、2、3、4瘤体体积均较干预前小,且治疗组1、2、3较对照组瘤体体积小(P均<0.05)。干预后第14、21天,治疗组3较治疗组1、2瘤体体积小(P均<0.05),治疗组1较治疗组4瘤体体积小(P均<0.05)。HE染色后光镜下可见各治疗组血管瘤内皮细胞分散凌乱、界限不清,且普萘洛尔浓度越高,对内皮细胞增殖抑制作用越明显。干预后第7、14、21天,治疗组1、2、3及对照组两两相比,治疗组1与治疗组4相比,裸鼠体质量比较差异无统计学意义。结论成功建立BALB/c裸鼠血管瘤模型;普萘洛尔可抑制模型裸鼠瘤体生长,对裸鼠机体无明显损害,且腹腔注射较灌胃效果显著。

Objective To investigate the effect of propranolol on the growth of transplanted hemangioma in BALB/c nude mice.Methods Infantile hemangioma was transplanted into BALB/c nude mice to establish the hemangioma-bearing models.Forty infantile hemangioma-bearing nude mice models were divided into five groups on the 45th day after implantation.Models in the treatment groups 1,2,3 received 0.01%,0.05%,and 0.1%propranolol(with 0.4 mL in each)by intraperitoneal injection,models in the treatment group 4 received 0.01%propranolol 0.4 mL by oral administration,while the models in the control group received sterilized normal saline 0.4 mL by intraperitoneal injection.They were all treated once a day for a week.Weight of mice and tumor volume in each group were tested and compared on the 7th,14th and 21st days after propranolol intervention.On the 22nd day of intervention,the tumors were gained and stained by HE staining to observe and compare the pathological changes.Results On the 7th,14th and 21st days after intervention,the tumor volume of treatment groups 1,2,3 and 4 was smaller than that before intervention,and the tumor volume of treatment groups 1,2 and 3 was smaller than that of control group(all P<0.05).On the 14th and 21st day after the intervention,the tumor volume of treatment group C was smaller than that of treatment groups 1 and 2(all P<0.05),and that of treatment group 1 was smaller than that of treatment group 4(P<0.05).After HE staining,the endothelial cells of hemangioma in each treatment group were scattered and disordered,and the boundary was not clear,and the higher the concentration of propranolol,the more obvious the inhibition of endothelial cell proliferation.On the 7th,14th and 21st days after the intervention,there was no significant difference in the weight of nude mice between the treatment groups 1,2,3 and control group.Conclusions The hemangioma models in BALB/C nude mice are established successfully,propranolol can inhibit the growth of tumor in nude mice,and the effect of intraperitoneal injection is better than that of gavage.