MAPK和PI3K调节缺氧诱导因子2α对慢性阻塞性肺疾病的作用

The role of MAPK and PI3K regulation of hypoxia inducible factor 2α on chronic obstructive pulmonary disease

目的探讨缺氧诱导因子2α(HIF-2α)、丝裂原活化蛋白激酶(MAPK),磷酸肌醇3-激酶(PI3K)的表达变化在缺氧性肺动脉高压(HPH)中的作用和意义。方法选择COPD患者(24例)和非COPD对照组(28例)患者为研究对象,行HE染色检测两组患者肺小动脉形态学改变,应用免疫组化检测肺小动脉壁内P-AKT、P-ERK、P-JNK、P-P38表达水平,应用原位杂交和免疫组化检测肺小动脉壁内HIF-2α的表达水平。结果 COPD患者管壁面积与管总面积比值及肺小血管中膜厚度均较对照组增高(P<0.01)。COPD患者肺小血管壁P-ERK以及P-AKT和HIF-2α基因表达水平较对照组患者肺血管壁内增强,而P-JNK、P-P38表达水平较对照无明显变化。结论 MAPK信号通路和磷酸肌醇3-激酶(PI3K)信号通路以及HIF-2α可能参与了COPD患者HPH的发生。

Objective To explore the role and significance of MAPK,PI3K and HIF-2α expression in Hypoxie pulmonary hypertension （HPH）. Methods Selected COPD and nomal patients as research project, small pulmonary arterial morphologic changes were detected by HE staining,the expression levels of P-AKT, P-ERK,P-JNK,P-P38 were detected by immuno- histochemieal detection,the expression levels of HIF-2α were detected in situ hybridization and immunohistochemistry detection. Results Film thickness,wall area to total area ratio of patients with COPD increased than the control group（P 〈 0.01 ）. P-ERK and P-AKT and HIF-2α gene expression level of patients with COPD were more enhanced than control group,but the expression of P-JNK and the P-P38 level had no significant change. Conclusion Differential expression of P-ERK,P-AKT and HIF-2α may involved in the occurrence of HPH of COPD patients.