普萘洛尔治疗婴幼儿增殖期血管瘤的实验研究

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1、中图分类号：R89；R36；R39硕士学位论文普萘洛尔治疗婴幼儿增殖期血管瘤的实验研究院（系）、所临床医学院研究生姓名刘大旭学科、专业外科学导师姓名刘铭彭强二Ο一二年四月目录1普萘洛尔治疗婴幼儿增殖期血管瘤的实验研究„„„„„„„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„31.2英文摘要„„„„„„„„„„„„„„„„„„„„„51.3前言„„„„„„„„„„„„„„„„„„„„„„„71.4材料与方法„„„„„„„„„„„„„„„„„„„„91.5结果„„„„„„„„„„„„„„„„„„„„„„„171.6讨论„„„„„„

2、„„„„„„„„„„„„„„„„„221.7结论„„„„„„„„„„„„„„„„„„„„„„„261.8参考文献„„„„„„„„„„„„„„„„„„„„„271.9英汉缩略词对照表„„„„„„„„„„„„„„„„„302致谢„„„„„„„„„„„„„„„„„„„„„„„213普萘洛尔治疗婴幼儿血管瘤的研究进展（综述）„„„„„„„32普萘洛尔治疗婴幼儿增殖期血管瘤的实验研究摘要目的：探讨普萘洛尔对婴幼儿增生期血管瘤的治疗作用及可能机制。方法：用手术切除的婴幼儿血管瘤新鲜组织块移植于裸鼠，建立血管瘤动物模型；于移植后第45天，将移植瘤组织均成活

3、的实验裸鼠22只分为2组：组1(普萘洛尔治疗组)，组2(生理盐水对照组)，每组11只，分别应用普萘洛尔和生理盐水治疗干预，观察比较移植瘤的生长情况；在首次药物干预后的第15天，将实验裸鼠用颈椎脱臼法处死，切取移植的瘤体组织。免疫组化法检测移植瘤组织中血管内皮细胞MVD值，CD34，Ki-67，Bcl-2，VEGF的表达情况，TUNEL法检测移植瘤组织中细胞的凋亡情况；酶联免疫吸附法检测cAMP浓度及PKA活性的变化。结果：1.药物干预后的l周、2周，普萘洛尔组与生理盐水组比较，两组移植瘤的体积出现显著差异(P<0.05)。普萘洛尔组瘤体组织颜

4、色苍白，血供较差，体积明显缩小，质地变硬。生理盐水组瘤体组织的颜色红润，血供良好，体积变化不明显，较有弹性。光镜下见，普萘洛尔组瘤体组织以纤维脂肪组织为主，血管内皮细胞稀疏分散，血管壁变形、塌陷，管腔结构有破坏征象；而生理盐水组可见毛细血管增生丰富，未见血管壁及管腔结构有破坏征象。2.免疫组化检测：普萘洛尔组MVD值，CD34、Ki-67、Bcl-2、VEGF的表达均明显低于生理盐水组，组间差异显著(P<0.05)；TUNEL法检测普萘洛尔组细胞凋亡指数明显高于生理盐水组，两组间有显著差异(P<0.05)，且普萘洛尔组Bcl-2阳性指数与细胞

5、凋亡指数之间呈显著负相关(γ=0.719，P<0.01)。3.酶联免疫吸附法检测普萘洛尔组cAMP浓度和PKA活性明显低于生理盐水组，两组间有明显差异(P<0.05)；且普萘洛尔组cAMP浓度和PKA活性变化呈正相关(γ=0.863，P<0.01)结论：1.普萘洛尔对婴幼儿增殖期血管瘤有明显的治疗作用。2.普萘洛尔可能诱导血管瘤血管内皮细胞凋亡，抑制其增殖，促进瘤体消退。3.普萘洛尔可能通过抑制cAMP／PKA信号通路对ERK／MAPK信号通路的激活，从而抑制增殖期血管瘤VEGF的分泌。关键词：普萘洛尔；婴幼儿血管瘤；内皮细胞；细胞凋亡；cA

6、MP／PKA信号通路PropranololtreatmentofinfantileproliferatinghemangiomasexperimentalstudyAbstract:bjective:Explorepropranololtreatmentanditspossiblemechanismofproliferativehemangiomaoninfantsandyoungchildren.Methods:Surgicalresectionofinfantilehemangiomafreshtissueinnudemicetoesta

7、blishtheanimalmodelofvasculartumor.Experimentsinnudemice45daysaftertransplantation,thetransplantedtumorssurvived22dividedinto2groups,group1(propranololgroup),group2(salinecontrolgroup),n=11,respectively,applicationofpropranololandsalinetreatmentinterventions,andtoobservethe

8、comparisonoftransplantedtumorgrowth;15daysafterthefirstdrugintervention,theexperim