低氧性肺动脉高压患者肺小动脉壁Siah1表达情况及其临床意义

摘要

目的：探讨低氧性肺动脉高压（ HPH）患者肺小动脉壁Siah1表达情况及其临床意义。方法收集湖南省肿瘤医院胸外科2008-04-01至2009-03-31行肺叶切除术的肺鳞癌患者36例，将除肺鳞癌外无其他肺部疾病患者12例纳入对照组，COPD非肺动脉高压患者12例纳入COPD组，COPD并HPH患者12例纳入PH组。收集患者肺组织，观察其肺血管重塑指标〔肺小动脉管壁厚度/血管外径（ WT%）、肺小动脉管壁面积/管总面积（ WA%）、肺小动脉管腔面积/管总面积（ LA%）〕，采用原位杂交法与免疫组织化学法检测肺小动脉壁Siah1 mRNA及其蛋白表达情况。结果光镜下可见对照组患者肺小动脉管壁薄，管腔大；COPD组患者肺小动脉管壁出现增厚，管腔狭窄；PH组患者肺小动脉管壁厚度进一步增加，管腔明显变窄。COPD组患者WA%、WT%高于对照组，LA%低于对照组（ P<0.05）；PH组患者WA%、WT%高于COPD组，LA%低于COPD组（P<0.05）。原位杂交结果显示，对照组患者肺小动脉壁Siah1 mRNA呈低表达，COPD组、PH组患者肺小动脉壁Siah1 mRNA表达逐渐增高。免疫组织化学结果显示，对照组患者肺小动脉壁Siah1蛋白呈低表达，COPD组、PH组患者肺小动脉壁Siah1蛋白表达逐渐增高。PH组患者肺小动脉壁Siah1 mRNA相对表达量及其蛋白水平高于COPD组，COPD组高于对照组（ P<0.05）。直线相关分析结果显示，Siah1蛋白水平与Siah1 mRNA相对表达量呈正相关（ r =0.873，P <0.01）；Siah1 mRNA 相对表达量与 WA%、WT%、肺动脉收缩压（PASP）均呈正相关（r 值分别为0.797、0.845、0.728，P <0.01），Siah1蛋白水平亦与WA%、WT%、PASP呈正相关（r值分别为0.791、0.791、0.704，P<0.01）。结论 HPH患者肺小动脉壁Siah1呈高表达，且肺小动脉壁Siah1表达与低氧性肺血管重塑及PASP有关，可能机制为慢性肺泡性低氧上调患者肺小动脉壁Siah1表达，进而参与HPH的发病。%Objective To investigate the expression of Siah1 of pulmonary arteriole walls and its significance in patients with hypoxic pulmonary hypertension. Methods From 2008-04-01 to 2009-03-31,a total of 36 lung squamous carcinoma patients undergoing pulmonary lobectomy were selected in the Department of Thoracic Surgery,Hu'nan Provincial Tumor Hospital,thereinto 12 patients without other pulmonary disease were served as A group,12 patients with COPD were served as B group,12 patients with COPD and hypoxic pulmonary hypertension were served as C group. Pulmonary vascular remodeling index including WT%,WA%,LA% was compared among the three groups;insitu hybridization method was used to detect the Siah1 mRNA expression,and immunohistochemical method was used to detect the Siah1 protein expression. Results Light microscope found that,the pulmonary arteriole walls of A group was thin,and the lumen was big;the pulmonary arteriole walls of B group was thickening,and the lumen was narrow;the pulmonary arteriole walls of C group was more thickening than that of B group,and the lumen was obviously narrow. WA% and WT% of B group were statistically significantly higher than those of A group,while LA% of B group was statistically significantly lower than that of A group(P<0. 05);WA% and WT% of C group were statistically significantly higher than those of B group,while LA% of C group was statistically significantly lower than that of B group(P <0. 05). By insitu hybridization method and immunohistochemical method,Siah1 mRNA expression and protein expression of A group were low,and those of groups B and C were increasingly higher. mRNA relative expression and protein level of Siah1 of C group were statistically significantly higher than those of B group, and those of B group were statistically significantly higher than those of A group(P <0. 05). Linear correlation analysis showed that,mRNA relative expression of Siah1 was positively correlated with protein level of Siah1(r=0. 873,P<0. 01);mRNA relative expression of Siah1 was positively correlated with WA%,WT%,PASP,respectively(r =0. 797,0. 845,0. 728,P <0. 01);protein level of Siah1 was positively correlated with WA%,WT%,PASP,respectively(r =0. 791,0. 791,0. 704,P <0. 01). Conclusion The expression of Siah1 of pulmonary arteriole walls is high in patients with hypoxic pulmonary hypertension,and it is correlated with hypoxic pulmonary vascular remodeling and PASP;chronic alveolar hypoxia may induce the expression of Siah1 of pulmonary arteriole walls,and lead to hypoxic pulmonary hypertension at last.