NVP-BEZ235对低氧诱导下大鼠心肌及主动脉的影响  

Effects of NVP-BEZ235 on myocardium and aorta of hypoxia induced rats

作　　者：柴晓宇[1] 许萌[1] 杨雪[1] 马纬麟 刘新民[1] 

机构地区：[1]北京大学第一医院老年科,100034

出　　处：《国际心血管病杂志》2017年第4期226-230,共5页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81270114)

摘　　要：目的:评价磷脂酰肌醇3激酶(PI3K)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路双重抑制剂NVP-BEZ235对于低氧诱导下大鼠心肌及主动脉的影响。方法:低氧组和NVP-BEZ235干预组置于实验室特制的低压低氧仓内饲养,对照组于常氧环境中饲养。NVP-BEZ235干预组给予35 mg/kg NVP-BEZ23隔天灌胃,低氧组及对照组隔天给予生理盐水灌胃。21 d后计算大鼠右心室质量(RVW)/体质量(BW)值;各组大鼠左心室心肌组织行苏木素伊红染色,并测量心肌血管数量及血管内径;胸主动脉行苏木素伊红染色、Russell Movat染色及α-平滑肌肌动蛋白(α-SMA)免疫组织化学染色;检测大鼠血清中血管内皮生长因子(VEGF)水平。结果:(1)低氧组大鼠较对照组RVW/BW明显升高(P=0.0002),NVP-BEZ235干预组大鼠较低氧组RVW/BW明显降低(P=0.0021)。(2)左室心肌组织HE染色可见低氧组大鼠心肌细胞排列紊乱,细胞间隙增宽;NVP-BEZ235干预组心肌排列较整齐,细胞间距倾较低氧组有所减小;3组大鼠心肌血管数量及管径差异无统计学意义(P均>0.05)。(3)病理染色可见低氧组大鼠胸主动脉弹性纤维排列紊乱,局部胞浆空泡变;NVP-BEZ235干预组大鼠胸主动脉的改变较低氧组有所减轻。低氧组大鼠胸主动脉管壁中层α-SMA表达较对照组不均匀增加;NVPBEZ235干预组大鼠胸主动脉α-SMA表达较低氧组相对减少。(4)低氧组大鼠血清VEGF水平较对照组明显升高(P=0.0027),NVP-BEZ235干预组较低氧组VEGF水平明显降低(P=0.0060)。结论:NVP-BEZ235可以抑制低氧诱导下大鼠心肌及主动脉的改变,并抑制低氧诱导的血清VEGF的升高。Objective：To evaluate the effect of PI3K/mTOR dual inhibitor NVP-BEZ235 on the myocardium and aorta of hypoxia induced rats. Methods：Male SD rats in the hypoxia group and NVPBEZ235 intervention group were raised in the specific hypoxic incubator while the control group were raised in normoxia condition.NVP-BEZ235 intervention group received NVP-BEZ235（35 mg/kg）by intragastric administration every two days while the control group and hypoxia group received saline.After 21 days,the right ventricular weights（RVW）and body weights（BW）were measured and calculated for the ratio of RVW/BW.The myocardium tissues were stained by hematoxylin-eosin,and the amount and internal diameters of myocardial vessels were measured.The thoracic aorta tissues were processed by hematoxylin-eosin, Russell Movat and α-SMA immunohistochemical staining. Theserum VEGF levels of rats were detected by ELISA. Results：（1）The RVW/BW ratio of hypoxia group was significantly elevated compared with control group（P=0.0002）and the RVW/BW ratio was decreased in the NVP-BEZ235 intervention group when compared with hypoxia group（P=0.0021）.（2）The hematoxylin-eosin staining of left ventricular myocardial tissue of hypoxia group showed myocardial cells derangement and intercellular space widened;NVP-BEZ235 intervention group showed less myocardial derangement and intercellular space than hypoxia group.There was no significant difference of the quantity and internal diameter of myocardial vessels among groups（all P0.05）.（3）The pathological staining of thoracic aortic showed elastic fibers derangement and local cytoplasmic vacuolation in hypoxia group,while the changes in NVP-BEZ235 intervention group were relatively less.The expression ofα-SMA in the middle wall of thoracic aorta increased unevenly in hypoxia group while the expression ofα-SMA in NVP-BEZ235 intervention group was less than hypoxia group.（4）The serum VEGF level of hypoxia group was significantly higher than control group（P=0.0027）while the l

关 键 词：低氧 心肌 主动脉 血管内皮生长因子 

分 类 号：R54[医药卫生—心血管疾病]