慢性阻塞性肺疾病患者肺部丝裂原活化蛋白激酶、蛋白激酶B和缺氧诱导因子1α的表达  

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

作　　者：孔春初 戴爱国 

机构地区：[1]湖南省老年医院湖南省老年医学研究所呼吸疾病研究室,长沙410001

出　　处：《中华结核和呼吸杂志》2006年第6期372-375,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金资助项目(30570815;30270581);湖南省教育厅重点科研基金资助项目(02A047)

摘　　要：目的探讨丝裂原活化蛋白激酶(MAPK)、磷酸肌醇3激酶(PI3K)、缺氧诱导因子1α(HIF1α)的表达变化在缺氧性肺动脉高压(HPH)中的作用和意义。方法通过苏木精伊红(HE)染色检测慢性阻塞性肺疾病(COPD)患者和对照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磷酸化蛋白激酶B(p PKB)、磷酸化胞外信号调控激酶(p ERK)、磷酸化c Jun氨基端蛋白激酶(p JNK)、磷酸化p38(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HIF1α的表达水平。结果COPD患者管腔面积与管总面积比值(LA%,18±3)及肺小动脉中膜厚度[PAMT,(31±3)μm]均较对照组[30±5、(40±4)μm]显著增高(t=7.58、6.57,P均<0.01)。COPD患者肺小动脉壁p ERK蛋白、p PKB蛋白、HIF1α蛋白和HIF1αmRNA表达[均以吸光度(A)值表示]水平(0.164±0.012、0.113±0.009、0.232±0.008、0.154±0.013)较对照组(0.062±0.010、0.031±0.011、0.058±0.006、0.052±0.008)显著增强(t=23.18、21.03、62.14、2.44,P均<0.01),而p JNK、p P38蛋白表达(0.041±0.012、0.031±0.010)与对照组(0.048±0.013、0.028±0.007)比较差异均无统计学意义(P均>0.05)。相关分析表明HIF1α蛋白、HIF1αmRNA、p ERK蛋白和p PKB蛋白表达与COPD组LA%呈显著负相关(r=-0.920～-0.892,P均<0.05),与PAMT呈显著正相关(r=0.895～0.934,P均<0.05)。结论MAPK信号通路和PI3K信号通路以及HIF1α可能参与了COPD患者HPH的发生。Objective To investigate the expression of mitogen-actived protein kinase （MAPK）, phosphatidylinositol 3-kinase （PI3K） and hypoxia-inducible factor-1α （HIF-1α） in pulmonary artery of chronic obstructive pulmonary disease（ COPD）, and therefore to explore the possible roles of MAPK, PI3K and HIF-1α 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-1α in lung tissue was examined by in situ hybridization and immunohistoehemistry. 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）μm] than in the control[30± 5, （40 ±4）μm, t = 7. 58,6.57, all P 〈 0. 011. The expression levels of p-ERK protein, p-PKB protein, HIF-1α protein and HIF-1α 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-1α were negatively correlated with LA% （ r = - 0. 920 --0. 892, all P 〈 0. 05 ）, and positively correlated with PAMT（r =0. 895 -0. 934,ali P〈0. 05）. Conclusion Differential expression of p-ERK,p-PKB and HIF- 1α may be involved in the occurrence of HPH in COPD patients.

关 键 词：丝裂原活化蛋白激酶 磷酸肌醇3-激酶 缺氧诱导因子1Α 缺氧 高血压 肺性 

分 类 号：R563.9[医药卫生—呼吸系统]