低氧性肺动脉高压大鼠肺组织相关凋亡基因表达的研究

Expression of some apoptosis-related genes in the lung tissues of rats with hypoxic pulmonary hypertension

目的 探讨bcl 2、bax、Fas、FasL凋亡相关基因在低氧肺动脉高压大鼠肺组织中的表达及其与发病的关系。方法 60只Wistar大鼠随机分为 5组 :正常对照组 ;低氧肺动脉高压组 ;血晶素组 ;锡原卟啉组 ;低浓度CO组 ;每组 12只。采用组织的原位细胞凋亡、DNA片段检测 ,免疫组织化学染色 ,原位杂交等方法进行检测。结果 低浓度CO组和血晶素组肺组织有典型的DNA梯带 ,bcl 2、bax、Fas、FasL免疫组化显示的表达呈强棕黄色 ,比低氧组均显著升高 ,原位杂交可见 ,低浓度CO组和血晶素组肺内支气管和小血管壁细胞胞浆呈强的紫蓝色 ,bcl 2表达呈棕黄色 ,比低氧组降低 ,原位杂交可见呈紫蓝色。结论 CO可以调节bcl 2、bax、Fas和FasL凋亡基因的表达 ,而这些凋亡基因又通过不同途径参与低氧肺动脉高压肺组织的细胞凋亡的调节 ,并在慢性阻塞性肺疾病的发生与发展中发挥重要作用。

Objective To study the expressions of some apoptosis related to genes in lung tissues and their relationship to the pathogenesis in rats to hypoxic pulmonary hypertension (HPH). Methods A total of 60 rats were employed and equally divided into 5 groups, i.e. control, HPH, hemin, Tin Protoporphyrin (Snpp) and low concentration CO groups. Of them, the rats from middle 3 groups were treated with hypoxia under normal pressure for 7 h in every day, 3 weeks except Sunday. Hemin and Tin Protoporphyrin (Snpp) were given half an hour before hypoxia while low concentration CO after 2 h of hypoxia. The expression of bcl 2, bax, Fas and Fas ligand (FasL) were detected with immunohistochemical staining, in situ cell death detection, DNA fragment detection, and in situ hybridization. Results In low concentration CO and hemin group, typical DNA ladder bands and apoptotic cells were found in lung tissues, and the expressions of Fas, FasL, bax, and bcl 2 mRNA were increased in the epithelial cells of alveoli, vascular and bronchial walls. And the expression of bcl 2 mRNA was decreased than in hypoxic group. Conclusion CO can regulate the expression of bcl 2, bax, Fas and FasL, these apoptotic genes may involve in the regulation of cell apoptosis of lung tissues under HPH and play important roles in the genesis and development of chronic obstructive lung disorders.