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p53基因对肺血管重构的保护作用

发表时间:2015-03-15  浏览量:1724  下载量:595
全部作者: 李刚,朱耀斌,刘爱军,续玉林,李斌,刘迎龙
作者单位: 首都医科大学附属北京安贞医院小儿心脏中心,北京市心肺血管疾病研究所
摘 要: 目的:重度肺动脉高压(pulmonary arterial hypertension,PAH)的病理改变与恶性肿瘤具有较大相似性,研究旨在探索抑癌基因p53在重度PAH肺血管重构中的可能作用。方法:雄性SD大鼠40只,随机分为空白对照组、p53对照组、PAH组、p53预防组。肺叶切除联合野百合碱注射建立重度PAH模型,气管吸入法转染携带野生型p53基因的腺病毒(Adeno-p53)注射液。Western blotting检测肺组织p53蛋白表达,心导管法检测肺动脉平均压(mean pulmonary arterial pressure,mPAP),称重法检测右心肥厚指数(right ventricular hypertrophy index,RVHI),病理学分析中膜肥厚、内膜增生程度和肺小动脉平滑肌细胞增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达情况。结果:干预3周后,PAH组大鼠p53蛋白表达水平较空白对照组降低(P<0.05),而p53对照组和预防组蛋白表达水平均较空白对照组升高(P<0.05)。p53预防组mPAP和RVHI较PAH组降低(P<0.05),中膜肥厚和内膜增生程度较PAH组减轻。病变肺小动脉α-actin染色阳性,p53预防组大鼠肺小动脉PCNA阳性率较PAH组下降(P<0.05)。结论:p53在重度PAH形成过程中发挥重要作用,基因转染增加其表达可抑制肺动脉高压的形成,抑制平滑肌细胞增殖是其可能作用机制之一。
关 键 词: 外科学;肺动脉高压;p53基因;肺血管重构
Title: Protective effects of p53 gene in the pulmonary arterial remodeling
Author: LI Gang, ZHU Yaobin, LIU Aijun, XU Yulin, LI Bin, LIU Yinglong
Organization: Pediatric Cardiac Center, Beijing Anzhen Hospital of Capital Medical University, Beijing Insitute of Heart Lung and Blood Vessel Disease
Abstract: Objective: Similarities exist between cancer and pulmonary arterial hypertension (PAH), and the present research is to investigate the possible effects of an anti-oncogene p53 in the process of pulmonary arterial remodeling in PAH. Methods: Forty male SD rats were randomly divided into four groups including control group, p53 control group, PAH group and p53 preventive group. Severe pulmonary arterial hypertension was induced by monocrotaline injection one week following left pneumonectomy and Adeno-p53 (with wild type p53 gene) was transfected into lung by tracheal inhalation. p53 protein expression were detected by Western blotting analysis, mean pulmonary arterial pressure (mPAP) were measured by catheterization, the right ventricular hypertrophy index (RVHI) was evaluated by the ratio of right ventricular to left ventricular plus septum weight, media hypertrophy and neointimal formation were analyzed by pathological method. The proliferation of pulmonary smooth muscle cells were analyzed by stain for α-smooth muscle actin and proliferating cell nuclear antigen (PCNA) with immunohistochemical method in small pulmonary artery. Results: The expression of p53 protein were lower in the PAH group than that in the control group after 3 week treatment (P<0.05), while the level of p53 protein were increased in both p53 control group and p53 preventive group (P<0.05). The mPAP and right ventricular hypotrophy index (RVHI) decreased in p53 preventive group when comparing with PAH group (P<0.05), medial hypertrophy and intimal hyperplasia reduced. The positive α-actin staining were widely distributed on small pulmonary arteries, and the PCNA positive rate were lower in p53 preventive group than in PAH group (P<0.05). Conclusion: p53 played an important role in the development of severe PAH, and overexpression of p53 gene by transfection prevented the formation of severe PAH. Inhibition of the smooth muscle cells proliferation was one of its possible mechanism.
Key words: surgery; pulmonary arterial hypertension; p53 gene; pulmonary arterial remodeling
发表期数: 2015年3月第5期
引用格式: 李刚,朱耀斌,刘爱军,等. p53基因对肺血管重构的保护作用[J]. 中国科技论文在线精品论文,2015,8(5):417-424.
 
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