氯离子通道阻断剂对大鼠低氧性肺动脉高压的影响  

Effects of chloride channel blocker on hypoxia induced rat pulmonary hypertension

作　　者：莫碧文[1] 曾锦荣[1] 李国坚[1] 黄文新[1] 于方[2] 王绩英[1] 王昌明[1] 

机构地区：[1]桂林医学院附属医院呼吸内科 [2]华中科技大学同济医学院同济医院

出　　处：《中国临床药理学与治疗学》2006年第6期677-680,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(№30260040);广西"新世纪十百千人才工程"人选专项资金资助项目(№2001211);广西区教育厅资助项目(No桂教科研[2002]316)

摘　　要：目的:探讨氯离子通道阻断剂三苯氧胺(tamoxifen,TAM)对大鼠低氧性肺动脉高压的治疗效果。方法:雄性Wistar大鼠96只,随机分为:(1)治疗组(缺氧+三苯氧胺,H/Q):大鼠在常压缺氧(10%,每日8 h)箱内饲养,缺氧前3 d开始灌胃三苯氧胺0.4 mg.kg-1.d-1,每日1次;(2)缺氧组(H组):每日给予相等量的生理盐水,余同治疗组;(3)正常对照组(C组)。测定各组大鼠d 4、7、14、21右心室/(左心室+室间隔)厚度,多导生理记录仪记录肺动脉平均压(mPAP),图像分析仪测定血管管壁面积占管总面积的百分比(WA/TA)和血管管腔面积占管总面积的百分比(VA/TA)。结果:缺氧组d 7mPAP开始升高,d 21达高峰,治疗组同时间点明显低于缺氧组;缺氧组RV/(LV+S)d 14开始上升,d 21达高峰,治疗组同时间点明显低于缺氧组;缺氧组d 21的血管管壁面积占管总面积的百分比(WA/TA)显著高于d 21治疗组(P<0.05)。而缺氧组d 21的血管管腔面积占管总面积的百分比(VA/TA)显著低于d 21治疗组(P<0.05)。结论:氯离子通道阻断剂三苯氧胺可降低缺氧所致大鼠肺动脉压升高、改善右心室肥厚及肺小动脉增厚,对低氧性肺动脉高压有一定的治疗作用。AIM： To investigate the therapeutic effect of chloride channel blocker tamoxifen on hypoxia pulmonary hypertension in rats. METHODS： Sixty male Wistar rats were randomly divided into therapeutic group （H/Q group）, hypoxia group （ n group）, normal control group （ C group）. Mean pulmonary artery pressure（rnPAP）,the ratio of the weight of right ventricle to that of left ventricle plus septum[RV（LV ＋ S）], and the ratio of the pulmonary arteriole wall area to that of vascular total area（WA/ TA）, were measured at 4,7, 14,21 days. RESULTS： The mPAP began to increase from 7 days, and reached peak at 21 days in hypoxia group, however it is obviously lower in therapeutic group at same time. The ratio of RV （LV ＋ S） began to increase from 14 days, and reached peak at 21 days in hypoxia group, however it is obviously lower in therapeutic group at same time. The ratio of WA/ TA at 21 days in hypoxia group was significantly higher than therapeutic group , respectively（ P 〈 0.05）. The ratio of VA/TA at 21 days in hypoxia group was significantly lower than therapeutic group, respectively （ P 〈 0.05 ）. CONCLUSION： The data suggested Tamoxifen could reduce hypoxia-induced increased pulmonary artery pressure, inhibit hypoxia-induced hypertrophic right ventricle and pulmonary small artery thickness. Tamoxifen may be used in the treatment of hypoxia induced pulmonary hypertension.

关 键 词：三苯氧胺 肺动脉高压 低氧 

分 类 号：R965.1[医药卫生—药理学]