口服普萘洛尔对婴幼儿血管瘤相关生长因子及凋亡因子表达水平的影响  

Effect of propranolol on the expression of growth factors and apoptotic factors related to infantile hemangiomas

作　　者：李铭[1] 郭志辉[1] 谢义德[1] 周亚宽[1] 陈小松[1] 江成鸿[1] 詹明坤[1] 王立敏[1] 

机构地区：[1]福建医科大学附属协和医院整形外科,福州350001

出　　处：《解放军医学杂志》2015年第2期121-127,共7页Medical Journal of Chinese People's Liberation Army

基　　金：福建省医学创新课题(2012-CX-17);福建省教育厅资助省属高校项目(JK2012020)~~

摘　　要：目的观察口服普萘洛尔对婴幼儿血管瘤病灶内相关生长因子及凋亡因子表达水平的影响。方法选择2010年5月-2011年12月收治的年龄≤3个月、血管瘤病灶位于肢体或隐蔽部位、家属要求手术治疗但具备单独口服普萘洛尔治疗条件、排除用药禁忌证、先前未接受过任何治疗的病例作为研究对象,共39例。所有患者均在局麻下夹取血管瘤体组织活检,然后口服普萘洛尔(每次1mg/kg,每12h服药一次)8周,继而手术切除瘤体。通过HE染色观察用药前后组织结构及细胞形态的变化,采用免疫组化、实时荧光定量RT-PCR检测用药前后病灶组织内ADRB1、ADRB2、ERK、Akt、NF-κB、VEGFA、Cyclin D1、Cyclin E1、Ki-67、Bax、Bcl-2、caspase-8、Fas、Fas L、caspase-9、caspase-3表达水平的变化,并分别用CD34、Ki-67免疫组化染色及TUNEL染色检测用药前后病灶内新生血管密度(MVD)、细胞增殖情况(Ki-67阳性率)以及细胞凋亡指数。结果与用药前比较,口服普萘洛尔后血管瘤病灶内ADRB1、ADRB2、ERK、Akt、NF-κB、VEGFA、Cyclin D1、Cyclin E1、Ki-67、Bcl-2表达水平明显下降(P<0.01),Bax、caspase-3、caspase-9表达水平明显增高(P<0.01),Fas、Fas L、caspase-8表达水平无明显改变(P>0.05)。与用药前比较,用药后病灶内MVD、Ki-67阳性率明显下降(P<0.01),凋亡指数明显增高(P<0.01)。结论普萘洛尔可通过调节MAPKs和PI3K-Akt通路抑制血管瘤增殖,促进内源性凋亡,但对外源性凋亡途径无明显影响。Objective To investigate the effects ofpropranolol on the expression of growth factors and apoptotic factors related to infantile hemangiomas, and explore the underlying mechanisms for treatment of hemangiomas by propranolol. Methods Oral propranolol was administered to 39 patients ≤ 3 months with hemangiomas during the proliferative phase, and they were in accordance with the inclusion criteria of the treatment. Patients who had contraindications to treatment were excluded, and informed consent from their family members was obtained. Biopsy of the lesion under local anesthesia was done before medication. The oral dose of propranolol was lmg/kg per 12 hours. After 8 weeks of treatment, the hemangioma was resected. The specimens taken before and after treatment were scrutinized for changes in tissue structure and cell form after HE staining. The expressions of the proteins ADRB1, ADRB2, ERK, Akt, NF-gB, VEGFA, Cyclin D1, Cyclin El, Ki-67, Bax, Bcl-2, caspase-8, Fas, FasL, caspase-9, and caspase-3 in the focal tissue were determined with immunohistochemistry and real-time fluorescence quantitative RT-PCR. At the same time, the microvessel density （MVD） value, Ki-67 index and apoptosis index before and after treatment were also determined and compared using CD34, Ki-67 and TUNEL staining technique, respectively. Meanwhile, the mRNA expressions of these factors were assessed with quantitative real-time RT-PCR. Results After 8 weeks of treatment, all the protein content and mKNA expressions ofADRB1, ADRB2, ERK, Akt, NF-KB, VEGFA, Cyclin D1, Cyclin El, Ki-67, Bcl-2, and MVD value and Ki-67 index were decreased significantly （P〈0.01）, while the protein and mRNA expressions of Bax, caspase-3, caspase-9, and apoptosis index were increased significantly （P〈0.01）. However, there was no obvious change in the expressions of Fas, FasL and caspase-8 after treatment. Conclusion Propranolol can inhibit proliferation and promot intrinsic apoptotic pathway ofhemangioma through regulating the MAPKs and PI3K-Akt pa

关 键 词：普萘洛尔 血管瘤 血管生成蛋白质类 凋亡诱导因子 

分 类 号：R732.2[医药卫生—肿瘤]