内源性CO在缺氧性肺动脉高压大鼠肺血管重构中的作用  

THE ROLE OF ENDOGENOUS CARBON MONOXIDE IN VASCULAR REMODELING IN HYPOXIC PULMONARY HYPERTENSION

作　　者：甄国华 张珍祥[1] 徐永健[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院呼吸内科,湖北武汉430030

出　　处：《中国应用生理学杂志》2002年第4期374-377,共4页Chinese Journal of Applied Physiology

摘　　要：目的和方法 :应用逆转录聚合酶链式反应 (RT PCR)、双波长分光光度法、右心导管及维多利亚蓝染色方法 ,动态观察慢性缺氧不同时间点大鼠肺组织中诱导型血红素氧合酶 (HO 1)基因表达、内源性CO生成、肺动脉压力及构型的变化 ,探讨内源性CO在大鼠缺氧性肺动脉高压肺血管重构中的作用。结果 :①正常大鼠肺组织可表达少量HO 1mRNA ,缺氧 5、10、15d大鼠肺组织HO 1mRNA含量分别增加 2 .3、3.6、4 .0倍 (P <0 .0 1) ,动脉血中COHb分别较正常大鼠增加 1.9、2 .6和 2 .9倍 (P <0 .0 1或P <0 .0 5 ) ,同时RVSP升高。光镜下可见IAPA血管壁增厚 ,管腔变窄。②Hemin可使缺氧大鼠肺组织HO 1mRNA和动脉血中COHb保持在高水平 (分别高达正常对照组的 5 .2和 3.7倍 ,P <0 .0 1或P <0 .0 5 ) ,能部分地抑制缺氧时大鼠RVSP的升高 ,减轻IAPA的病理改变。结论 :在慢性缺氧性肺动脉高压大鼠肺组织中HO 1基因的表达增加 ,内源性CO生成增多。Hemin促进HO 1基因表达和内源性CO生成 ,可抑制肺动脉压升高 ,阻抑肺血管重构 。Aim: To investigate the expression of heme oxygenase 1 gene and production of endogenous carbon monoxide in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin, an inducer of heme oxygenase, on the expression of HO 1 gene and production of endogenous carbon monoxide and pulmonary hypertension. Methods: We recreated a rat model of hypoxic pulmonary hypertension by intermittent normal pressure hypoxia (10% O 2). The following assays were carried out: Reverse transcriptase polymerase chain reaction (RT PCR) were performed to determine the level of HO 1 mRNA in rat lung tissue, double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood, cardiac catheterization was used to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathologic changes of the intra acinar pulmonary arteries(IAPA). Results: ①There was low level of HO 1 mRNA in normal rat lung tissue, but the level of HO 1 mRNA increased by 2 4 times in the lung tissue of hypoxic rats ( P <0.01). The quantity of COHb was 2 3 times as those of control group ( P <0.01 or P <0.05). These were accompanied by the increase of RVSP and the thickness of IAPA. ②Hemin could maintain the HO 1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, ameliorated the pathologic changes of IAPA. Conclusion: The upregulation of the expression of HO 1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension.

关 键 词：内源性CO 缺氧性肺动脉高压 大鼠 肺血重构 作用 

分 类 号：R543.2[医药卫生—心血管疾病]