调控P13K／Akt信号通路对裸鼠移植血管瘤的影响  

Effects of regulating PI3K/Akt signaling pathway on xenograft model of hemangioma in nude mice

作　　者：彭岗[1,2] 俞松[1] 陆建国[1] 闫陶然 卓金伟 柳望舒 徐艳朋[1] 

机构地区：[1]遵义医学院附属医院小儿矫形外科,563003 [2]贵州省人民医院小儿外科

出　　处：《中华小儿外科杂志》2015年第9期671-674,共4页Chinese Journal of Pediatric Surgery

基　　金：国家自然科学基金（81160330,81460476）;贵州省省长资金项目[黔省专合字（2010）67号]

摘　　要：目的观察人血管瘤裸鼠移植模型中P13Kp85、p-Akt表达，并进行正负调控，探讨PDK／Akt信号通路在小儿血管瘤演变过程中的作用。方法建立血管瘤裸鼠移植模型，生长45d后，将移植成功标本48例，按区组随机平均分成3组。其中，对照组每个瘤体内注射生理盐水0．05ml;正性调控组每个瘤体内注射0．5μmol／L的胰岛素样生长因子0．05ml；负性调控组每个瘤体内注射25μmol／L的LY2940020．05ml。于药物注射当日（用药前）、注射后3d、1周、2周肉眼大体观察移植瘤形态变化，光镜观察移植瘤组织结构变化，同期免疫组化检测P13Kp85、p-Akt蛋白的分布及表达情况，RT-PCR检测PDKp85mRNA、p-AktmRNA的表达情况。结果负性调控组P13Kp85、p-Akt阳性表达率分别为80．00％和86．67％，而对照组及正性调控组P13Kp85及p-Akt阳性表达率均为100％。负性调控组PDKp85、p-Akt表达均较对照组降低，差异有统计学意义（P〈0．05或0．01），瘤体呈消退表现；正性调控组P13Kp85、p-Akt表达均较对照组增高，差异有统计学意义（P〈0．05或0．01），血管瘤瘤体呈增生表现；P13Kp85与p-Akt的表达呈正相关。结论P13K／Akt信号通路可能参与了裸鼠移植血管瘤增生与消退的调控；LY294002、胰岛素样生长因子可以通过干预P13K／Akt信号通路中相应的靶点，抑制或激活P13K／Akt信号通路来促使瘤体消退及增生。Objective To explore the expressions of phosphatidylinositol 3-kinase p85 （PI3Kp85） and protein kinase B （Akt） in nude mice model of human hemangioma xenogra{t and examine the role of PI3K/ Akt signaling pathway in evolution process of hemangioma in children. Methods The surgical specimens of proliferating hernmagioma were harvested from a male 3-month-old infant. The tissues were sliced into small pieces 5 mm 4 mm 3 mm in size and grafted subcutaneously into nude mice. After growing for 45 days, a total of 48 cases of successful xenograft specimens were randomized into 3 groups： 0. 05 ml saline was intratumorally injected for each tumor in control group, 0. 05 ml insulin-like growth factor （0. 5 μnol/L） intratumorally injected for each tumor in positive control group and 0. 05 ml LY294002 （25 μol/L）was intratumorally injected for each tumor in negative control group. At the day of injection and 3 days, 1 week and 2 weeks post-injection, the morphological changes of hemangioma xenografts were visually observed and their structural changes observed microscopically. The expressions of PI3Kp85, p-Akt protein were determined by immunohistochemistry. And the expressions of PI3Kp85 mRNA and p-Aktm RNA were observed by reverse transcription-polymerase chain reaction （RT-PCR）. Results The positive expression rates of PI3Kp85 and p-Akt were 100% in control and positive control groups. And the positive expression rates were 80. 00% and 86. 67~ in negative control group. The stains of PI3Kp85 and p-Akt became weaker significantly in negative control group. And significant differenees in PBKp85 and p-Akt stains existed between negative control and control groups （P〈 0. 05 or 0. 01） and then xenograft specimens showed regression. The stains of PI3Kp85 and p-Akt turned stronger significantly in positive control group. Significant differences of PI3Kp85 and p-Akt stains existed between positive control and control groups（P〈 0. 05 or 0. 01）. The xenograft specimens showed prolifemtiorL And the

关 键 词：血管瘤 模型 动物 信号传递 基因表达调控 

分 类 号：R732.2[医药卫生—肿瘤] R-332[医药卫生—临床医学]