mTOR信号通路活化促进门静脉高压大鼠肠系膜血管新生的实验研究  

Experimental study on activation of mTOR signaling pathway promoting mesenteric angiogenesis in portal hypertensive rats

作　　者：陈云扬[1] 王维杰[2] 王化恺[1] 施敏敏[1] 张明钧[1] 严佶祺[1] 杨卫平[1] 彭承宏[1] 李宏为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院外科,上海200025 [2]郑州大学第一附属医院外科,河南郑州450052

出　　处：《外科理论与实践》2015年第3期221-225,共5页Journal of Surgery Concepts & Practice

基　　金：国家自然科学基金(81070358)

摘　　要：目的:探讨m TOR信号通路在门静脉高压大鼠肠系膜中的活化状态,研究m TOR信号通路的激活参与门静脉高压大鼠肠系膜血管新生,及其可能机制。方法:雄性SD大鼠随机分为假手术组和模型组,采用胆道结扎离断和部分静脉结扎制备门静脉高压症模型。通过组织病理学和血流动力学分别评估肠系膜血管新生和门静脉压力。采用Western印迹法分别测定血管新生标志物血管内皮生长因子(VEGF)和m TOR信号通路标志物P70S6K和4EBP1的表达。结果:术后3周,两种大鼠模型脾脏肿大、肠系膜血管新生和门静脉压力显著增高(P<0.01);VEGF蛋白表达量、P-P70S6K和P-4EBP1的相对表达量也显著增高(P<0.01)。结论:m TOR信号通路活化促进门静脉高压大鼠肠系膜血管新生,阻断该通路可能有助于抑制侧支循环的建立,降低内脏血流高动力循环。Objective To investigate the activity of m TOR signaling pathway in mesenteric tissue of portal hypertensive rats and the activation of m TOR signaling in the mesenteric angiogenesis as well as the mechanism. Methods Portal hypertension was induced by bile duct ligation（BDL） and partial portal vein ligation（PPVL）. Male SD rats were randomly divided into sham-operated group, BDL group and PPVL group. Mesenteric angiogenesis and portal vein pressure were accessed by histopathology and hemodynamics, respectively. Expressions of VEGF, P70S6 K and 4EBP1 were examined by Western blot assay. Results Splenomegaly, mesenteric angiogenesis and increase in portal pressure were found in both models after BDL or PPVL 3 weeks later（P〈0.01）. Expressions of VEGF, P-P70S6 K and P-4EBP1 increased significantly（P〈0.01）. Conclusions It is suggested that the activation of m TOR signaling pathway promotes mesenteric angiogenesis in portal hypertensive rats. Blocking the signaling pathway could be beneficial in inhibiting the establishment of portosystemic collateral circulation and reducing hyperdynamic splanchnic circulation.

关 键 词：MTOR信号通路 门静脉高压 肠系膜血管新生 侧支循环 

分 类 号：R657.34[医药卫生—外科学]