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

Expression of Siah1 of Pulmonary Arteriole Walls and Its Significance in Patients with Hypoxic Pulmonary Hypertension

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.