普萘洛尔治疗婴儿增殖期血管瘤的实验研究.pdf

目 录 1 普萘洛尔治疗婴幼儿增殖期血管瘤的实验研究„„„„„„„„1 1.1 中文摘要„„„„„„„„„„„„„„„„„„„„„3 1.2 英文摘要„„„„„„„„„„„„„„„„„„„„„5 1.3 前言„„„„„„„„„„„„„„„„„„„„„„„7 1.4 材料与方法„„„„„„„„„„„„„„„„„„„„9 1.5 结果„„„„„„„„„„„„„„„„„„„„„„„17 1.6 讨论„„„„„„„„„„„„„„„„„„„„„„„22 1.7 结论„„„„„„„„„„„„„„„„„„„„„„„26 1.8 参考文献„„„„„„„„„„„„„„„„„„„„„27 1.9 英汉缩略词对照表„„„„„„„„„„„„„„„„„30 2 致谢„„„„„„„„„„„„„„„„„„„„„„„21 3 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(P0.05)。普萘 洛尔组瘤体组织颜色苍白，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(P0.05)；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 (P0.05)，且普萘洛尔组Bcl-2 阳性指数与细胞凋亡指数之间呈显著 负相关 (γ=0.719，P0.01)。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 (P0.05)；且普萘洛尔组cAMP 浓度和PKA 活性变化呈正相关 (γ =0.863，P0.01)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；cAMP ／PKA信号通路 Propranolol treatment of infantile proliferating hemangiomas experimental study Abstract:bjective : Explore propranolol treatment and its possible mechanism of proliferative hemangioma on infants and young children. Methods : Surgical resection of infantile hemangioma fresh tissue in nude mice to establish the animal model of vascular tumor. Experiments