缺氧和DDPH对人胚肺成纤维细胞前胶原mRNA表达的影响

EFFECTS OF HYPOXIA AND DDPH ON THE EXPRESSION OF PROCOLLAGEN mRNA IN HUMAN EMBRYONIC LUNG FIBROBLASTS

用核酸原位杂交和图像分析等方法，观察直接缺氧（Ｈ）和缺氧猪肺动脉内皮细胞条件培养液（ＨＥＣＣＭ）对人胚肺成纤维细胞（ＫＭＢ１７）的前胶原ｐｒｏα１（Ⅰ），ｐｒｏα１（Ⅲ）ｍＲＮＡ表达和抗高血压药１－（２，６－二甲基苯氧基）－２－（３，４－二甲氧基苯乙氨基）丙烷盐酸盐（ＤＤＰＨ）对此过程的影响。结果发现，Ｈ和ＨＥＣＣＭ均可使ＫＭＢ１７的两型前胶原ｍＲＮＡ表达量增高，明显高于对照组（Ｐ＜０．０１）。ＤＤＰＨ对ＨＥＣＣＭ组细胞的Ⅰ，Ⅲ两型前胶原ｍＲＮＡ表达增高均有显著的抑制作用（抑制率分别为－４３．９７％和－５６．２２％），而对Ｈ组仅抑制ｐｒｏα１（Ⅰ）前胶原ｍＲＮＡ的过量表达（－５３．５８％）。提示缺氧可直接或通过肺动脉内皮细胞的介导，促进人胚肺成纤维细胞的Ⅰ、Ⅲ两型前胶原ｍＲＮＡ表达。

The effects of hypoxia and the medium conditioned by hypoxically cultured porcine pulmonary arterial endothelial cells (HECCM) on the expression of proα 1(Ⅰ) and proα 1(Ⅲ) procollagen mRNA in human cmbryonic lung fibroblasts (KMB 17 ) were studied with in situ hybridization and image analysis. The influence of antihypertensive drug DDPH on this process was also investigated. The results showed that both direct hypoxia and HECCM could stimulate the expression of proα 1(Ⅰ) and proα 1(Ⅲ) procollagen mRNA by KMB 17 cells, and the quantity of the expression of both types of procollagen mRNA by these cells was significantly greater than that of the control groups ( P <0 01). DDPH obviously inhibited the expression of both types of procollagen mRNA in HECCM group by 43 97% and 56 22% respectively. But it only inhibited the over expression of proα 1(Ⅰ) procollagen mRNA in hypoxic group. These results suggest that hypoxia can stimulate the expression of proα 1(Ⅰ) and proα 1(Ⅲ) procollagen mRNA by KMB17 cells directly or mediated by the pulmonary arterial endothelial cells and DDPH can inhibit this process at the level of gene transeription.