中文摘要：

目的探讨低体积分数氧（低氧）性肺动脉高压大鼠在肺动脉高压、肺血管重构发生发展过程中,肺组织Notch信号的改变。方法Wistar雄性成年大鼠35只随机分为7组,予低氧处理,在低氧0 d、1 d、3 d、1周、2周、3周、4周测定平均肺动脉压后处死,测定其右心指数;并取其右肺作石蜡切片,HE染色,观察肺血管重构情况;同时采用荧光定量PCR法测定其左肺组织中Notch1、2、3、4受体mRNA及HERP1、2 mRNA水平。采用SPSS12.0软件进行统计学分析。结果低氧大鼠平均肺动脉压在低氧后2周达高峰,此后一直维持在一个较高水平,但其右心指数进行性升高;随缺氧时间延长,肺小动脉管壁厚度增加,肺血管发生重构。肺组织Notch1、3、4受体mRNA和HERP1 mRNA水平呈时间依赖性变化,Notch1、4受体mRNA和HERP1 mRNA在低氧后2周达高峰,Notch3受体mRNA在低氧后1周达高峰,总体变化趋势与肺动脉压趋近一致。而Notch2受体mRNA无明显改变。结论Notch信号随低氧性肺动脉高压的发生、发展呈时间依赖性,与肺动脉压的变化趋近一致,提示Notch参与了肺动脉高压肺血管重构过程。

英文摘要：

Objective To explore the change of Notch signal in lung tissue of rat with pulmonary hypertension （ PH ） induced by hypoxia during the development and progression of PH and pulmonary vascular remodeling. Methods Thirty - five Wistar male rats were randomly assigned to 7 groups. In addition to a control group,there were 6 hypoxie PH model groups which were treated in hypoxie environment for 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, respectively. Mean pulmonary arterial pressure（mPAP） and fulton index of hypoxic rats were measured at those different time points. Paraffin sections and HE dying of their right lungs were made in order to observe their pulmonary vascular remodeling. Notch 1,2,3,4 receptors mRNA and HERP 1,2 mRNA levels of their left lungs were detected by real time fluorescent quantitation. Software of SPSS 12.0 was used to analyze all data. Results The mPAP of hypoxie rats rose to the peak at 2 weeks point, and then maintained at a higher level, but their fulton index continued to advance. The variations of mRNA of Notch 1 ,3, 4 receptors mRNA and HERP 1 mRNA were time - dependent, that was, the levels of Notch 1,4 receptors mRNA and HERP 1 mRNA peaked at 2 weeks after hypoxic, while when it came to Notch 3 receptor, it peaked in 1 week after hypoxie. Totally the trends of these alterations were coincident with the variations of mPAP. The level of Notch 2 receptor mRNA showed no obvious change. Conclusions During the development and progression of hypoxie PH, Notch signal alter in a time -dependent manner, and the alteration trends are coincident with the variations of mPAP. Notch signaling orobablv involves in the pathogenesis of pulmonary vascular remodeling of PH.