[丝裂原活化蛋白激酶、磷脂酰肌醇3激酶及缺氧诱导因子-1α在慢性阻塞性肺疾病患者肺动脉中的表达]

[Expression of mitogen-actived protein kinase, phosphatidylinositol 3-kinase and hypoxia-inducible factor-1alpha in pulmonary arteries of patients with chronic obstructive pulmonary disease].

作者信息

Kong Chun-chu, Dai Ai-guo

机构信息

Department of Respiratory Disease Research, Hunan Institute of Gerontology, Hunan Geriatric Hospital, Changsha 410001, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2006 Jun;29(6):372-5.

PMID:17045016

Abstract

OBJECTIVE

To investigate the expression of mitogen-actived protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and hypoxia-inducible factor-1alpha (HIF-1alpha) in pulmonary artery of chronic obstructive pulmonary disease (COPD), and therefore to explore the possible roles of MAPK, PI3K and HIF-1alpha in the development of hypoxia-induced pulmonary hypertension (HPH).

METHODS

Small pulmonary arterial remodeling was observed by morphometric analysis in surgically removed lung tissues from COPD patients and control patients treated for lung tumors. The expression of p-ERK, p-JNK, p-P38, p-PKB and HIF-1alpha in lung tissue was examined by in situ hybridization and immunohistochemistry.

RESULTS

Morphometry analysis showed that the ratio of wall area to total area (WA%) and pulmonary artery media thickness (PAMT) were increased in COPD patients [18 +/- 3, (31 +/- 3) microm] than in the control [30 +/- 5, (40 +/- 4) microm, t = 7.58, 6.57, all P < 0.01]. The expression levels of p-ERK protein, p-PKB protein, HIF-1alpha protein and HIF-1alpha mRNA level (absorbance, A) were significantly higher in pulmonary artery walls of COPD patients (0.164 +/- 0.012, 0.113 +/- 0.009, 0.232 +/- 0.008, 0.154 +/- 0.013, respectively) as compared to those of the control (0.062 +/- 0.010, 0.031 +/- 0.011, 0.058 +/- 0.006, 0.052 +/- 0.008, respectively, t = 23.18, 21.03, 62.14, 2.44, all P < 0.01), while p-JNK and p-P38 protein levels in the control group (0.048 +/- 0.013, 0.028 +/- 0.007, respectively) and COPD patients (0.041 +/- 0.012, 0.031 +/- 0.010, respectively, all P > 0.05) were barely positive. The expression of p-ERK, p-PKB and HIF-1alpha were negatively correlated with LA% (r = -0.920 - -0.892, all P < 0.05), and positively correlated with PAMT (r = 0.895 - 0.934, all P < 0.05).

CONCLUSION

Differential expression of p-ERK, p-PKB and HIF-1alpha may be involved in the occurrence of HPH in COPD patients.

摘要

目的

研究丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3激酶（PI3K）及缺氧诱导因子-1α（HIF-1α）在慢性阻塞性肺疾病（COPD）患者肺动脉中的表达情况，从而探讨MAPK、PI3K及HIF-1α在缺氧性肺动脉高压（HPH）发生发展中的可能作用。

方法

通过形态计量学分析，观察手术切除的COPD患者及因肺部肿瘤接受治疗的对照患者肺组织中的小肺动脉重塑情况。采用原位杂交和免疫组化法检测肺组织中p-ERK、p-JNK、p-P38、p-PKB及HIF-1α的表达。

结果

形态计量学分析显示，COPD患者的壁面积与总面积之比（WA%）及肺动脉中膜厚度（PAMT）[分别为18±3，（31±3）μm]高于对照组[分别为30±5，（40±4）μm，t = 7.58，6.57，P均<0.01]。COPD患者肺动脉壁中p-ERK蛋白、p-PKB蛋白、HIF-1α蛋白表达水平及HIF-1α mRNA水平（吸光度，A）[分别为0.164±0.012，0.113±0.009，0.232±0.008，0.154±0.013]显著高于对照组[分别为0.062±0.010，0.031±0.011，0.058±0.006，0.052±0.008，t = 23.18，21.03，62.14，2.44，P均<0.01]，而对照组（分别为0.048±0.013，0.028±0.007）及COPD患者（分别为0.041±0.012，0.031±0.010）中p-JNK和p-P38蛋白水平几乎呈阴性（P均>0.05）。p-ERK、p-PKB及HIF-1α的表达与WA%呈负相关（r = -0.920～-0.892，P均<0.05），与PAMT呈正相关（r = 0.895～0.934，P均<0.05）。