氯离子通道阻断剂对大鼠低氧性肺动脉高压的影响

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。

Effects of chloride channel blocker on hypoxia induced rat pulmonary hypertension

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(H group),normal control group(C group).Mean pulmonary artery pressure(mPAP),the ratio of the weight of right ventricle to that of left ventricle plus septumRV(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.