糜蛋白酶在烟草烟雾诱导的仓鼠肺动脉高压中的作用  

Role of chymase in cigarette smoke-induced pulmonary hypertension in hamsters

作　　者：米日古丽 王娟[2] 郭李平[2] 常建梅[2] 李鹏[2] 韩敏[2] 韩素霞[2] 

机构地区：[1]新疆自治区人民医院心血管内科,乌鲁木齐830000 [2]新疆医科大学第五附属医院心血管内科,乌鲁木齐830000

出　　处：《新医学》2014年第9期580-585,共6页Journal of New Medicine

基　　金：国家自然科学基金(81060023)

摘　　要：目的探讨糜蛋白酶在烟草烟雾所诱导的肺动脉重构和肺动脉高压中的作用。方法将仓鼠暴露在烟草产生的烟雾中(烟雾暴露组,n=6),4个月后,使用免疫组织化学法、蛋白免疫印迹法、放射免疫学测定、反转录PCR等测定仓鼠肺的形态学和肺组织的生物化学改变。对烟雾暴露组与对照组(n=6)上述指标进行比较。结果长期烟草烟雾暴露使仓鼠右心室收缩压升高,肺小动脉中层细胞肥大,同时肺组织糜蛋白酶活性及合成增加,血管紧张素Ⅱ(AngⅡ)水平升高(与对照组比较,P均﹤0.05)。糜蛋白酶抑素(chymostatin)可以降低烟草诱导的仓鼠肺组织中糜蛋白酶活性的增加和AngⅡ水平,改善肺小动脉的重构程度,降低右心室收缩压,但对仓鼠肺组织中血管紧张素转换酶(ACE)的活性无影响。结论长期烟草烟雾暴露可增加仓鼠肺中糜蛋白酶的活性及表达,激活的糜蛋白酶进一步诱导肺组织AngⅡ形成,这可能是烟草诱导的肺动脉高压发生机制的一部分。因此,糜蛋白酶抑素也许会对吸烟的肺动脉高压患者有益。Objective The aim of this study was to determine the potential role of chymase in cigarette smoke-induced pulmonary arterial remodeling and hypertension. Methods Hamsters were exposed to cigarette smoke for 4 months（ smoke-exposed group,n = 6）. After smoke exposure,lung morphology and tissue biochemical changes were examined using immunohistochemistry,Western blotting,radioimmunoassay and reversetranscription polymerase chain reaction. Comparison of these indicators in the smoke-exposed group and the control group（ n = 6）. Results Chronic exposure to cigarette smoke significantly induced elevation of right ventricular systolic pressures and medial cells hypertrophy of pulmonary arterioles in hamsters,concurrent with an increase in the activity and synthesis of chymase in the lung. Elevated Ang Ⅱ levels was also observed in smoke-exposed lungs（ compared with the control group,all P〈0. 05）. Chymostatin could reduce the cigarette smoke-induced increase in chymase activity and Ang Ⅱ concentration in the lung,and attenuated the right ventricular systolic pressures elevation and the remodeling of pulmonary arterioles. Chymostatin did not affect angiotensin converting enzyme（ ACE） activity in hamster lungs（ compared with pure smoke-exposed group,all P〈0. 05）. Conclusions Chronic exposure to cigarette smoke can increase the activity and expression of chymase in hamster lungs. The capability of activated chymase to induce Ang Ⅱ formation may be part of the mechanism for smoking-induced pulmonary vascular remodeling. Thus,our study implies that blockade of chymase might provide benefits to pulmonary arterial hypertension smokers.

关 键 词：糜蛋白酶 仓鼠 肺动脉高压 肺动脉重构 糜蛋白酶抑素 血管紧张素Ⅱ 

分 类 号：R96[医药卫生—药理学]