肺动脉高压大鼠肺组织Notch信号的改变

The Change of Notch Signal Rats in Lung Tissues of Pulmonary Hypertension

目的探讨肺动脉高压（pulmonary hypertension，PH）大鼠肺组织Notch受体的改变。方法构建肺切除＋野百合碱PH大鼠模型，与正常大鼠比较肺血管重构指标的改变。进行肺组织免疫组化Notch 1-Notch4受体染色和实时荧光定量PCR（RT—PCR）检测（Notch 1-Notch4）mRNA。结果肺切除＋野百合碱组大鼠平均肺动脉压力（mPAP）、右心指数[fulton index，RV／（LV＋S）]、肺小动脉中膜厚度百分比（WT，％）、非肌性小动脉肌化程度、管壁细胞增殖度，明显高于正常大鼠，差异有显著意义（P〈0．05），有新生内膜形成。肺组织免疫组织化染色，肺切除＋野百合碱组和正常对照组大鼠肺动脉均有Notch1，Notch3，Notch4受体表达，未见Notch2受体表达。Notch1表达于血管内皮细胞和平滑肌细胞，Notch3主要表达于平滑肌细胞，Notch4主要表达于内皮细胞。肺切除＋野百合碱组肺组织（Notch1～Notch4）mRNA水平高于正常对照组。结论Notch1，Notch3，Notch4表达于肺动脉，随着PH肺血管重构的发生，表达上调。Notch信号很可能参与了PH肺血管重构过程。

Objective To explore the change of Notch signal in rats＇ lung hypertension （PH）. Methods The PH models of rats were established by tissues of pulmonary pneumonectomy plus monocrotaline injection, which was compared indexes about pulmonary vascular remodeling with the group of normal rats. Their lung tissues were detected by immunohistoehemistry technique and real-time fluorescent quantitation RT-PCR for Notch 1, 2, 3 and 4 receptor. Results Those indexes of the model group were higher than the normal group, including mean pulmonary arterial pressure （mPAP）, fulton index [RV/（LV＋S）], percentage of small pulmonary arteries media thickness （WT,%）, muscularizition of non-musclirised pulmonary arterioles and extent of cellular proliferation in pulmonary arterioles （P〈0.05）. And neointima formation was observed in model group. By immunohistoehemistry staining, Notich 1, Notieh 3, Notich 4 receptor were positive in pulmonary arteries of the model group and the normal group. Notch 1 and 3 receptor were positive in smooth muscle cells of pulmonary arteries, and Notch 1 and 4 receptor were positive in endothelial cells of pulmonary arteries, while Notch 2 receptor was negative in pulmonary arteries. Notch 1, 2, 3 and 4 receptor mRNA levels in lung tissues of model group were higher than the normal group. Conclusion Notch 1, 3 and 4 receptor were expressed in pulmonary artery, which up-regulation seemed related to the development of pulmonary vascular remodeling during PH, and possibly involved in pulmonary vascular remodeling.