氟西汀对野百合碱诱导Wistar大鼠肺动脉和右心室构型重建的影响  

Effect of fluoxetine on monocrotaline-induced remodeling of pulmonary arteries and right ventricle in rats

作　　者：王韵[1] 刘明[2] 章新华[1] 王寒明[1] 王丹[1] 张洪艳[1] 白洋[1] 王怀良[1] 

机构地区：[1]中国医科大学临床药理教研室,辽宁沈阳110001 [2]中国刑警学院禁毒系,辽宁沈阳110035

出　　处：《解剖科学进展》2011年第5期428-431,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金资助项目(No.30572194;No.30973533)

摘　　要：目的研究氟西汀对野百合碱(monocrotaline,MCT)诱导Wistar大鼠肺动脉和右心室构型重建的影响。方法应用野百合碱建立大鼠肺动脉高压模型,40只Wistar大鼠均分为4组:对照组(control)、模型组(MCT)、氟西汀低剂量2mg/kg组(MCT+F2)和氟西汀高剂量10mg/kg组(MCT+F10),分别用多导生理记录仪记录肺动脉压和体循环血压。将肺和心脏组织固定、包埋,切片进行HE染色,观察肺动脉和心肌形态学改变。计算肺动脉中膜厚度百分比和右心指数。采用Western blotting方法检测右心室基质金属蛋白酶9(matrix metalloproteinases9,MMP9)的表达水平。结果与对照组相比,MCT诱发肺动脉高压,肺动脉重构,右心肥厚,心肌细胞损伤,右心室MMP9的蛋白表达明显增加。与MCT组相比,氟西汀剂量依赖性地降低以上各指标,且氟西汀高剂量组对其有明显的抑制作用(P<0.05)。结论氟西汀能有效减轻MCT诱导的大鼠肺动脉和右心室构型重建。Objective To investigate the effect of fluoxetine on monocrotaline （MCT）-induced remodeling of the pulmonary arteries and the right ventricle in rats. Methods Models of pulmonary arterial hypertension （PAH） were established by MCT. 40 Wistar rats were divided into four groups： control group, model group （MCT）, treatment group with fluoxetine at 2mg/kg （MCT＋F2） and at 10mg/kg （MCT＋F10） respectively. Pulmonary arterial pressure and systemic arterial pressure were recorded by the polygraph system. The lung and heart sections were stained with hematoxyline-eosine （HE）, followed by measurement of the percentage of medial wall thickness and right ventricular index. The protein expression of matrix metalloproteinases 9 （MMP9） in right ventricle was detected by western blotting. Results Compared with the control group, MCT caused pulmonary arterial hypertension, pulmonary arterial remodeling, right ventricular hypertrophy, myocardial injury and significantly increased expression of MMP9 in the right ventricle. Compared with the MCT group, fluoxetine dose-dependently decreased the above indexes, and the inhibitory effect was markedly in MCT＋F10 group （ P 0.05）. Conclusion Fluoxetine effectively attenuated the remodeling of pulmonary arteries and right ventricle in rats.

关 键 词：氟西汀 肺动脉高压 野百合碱 肺血管重构 右心肥厚 WISTAR大鼠 

分 类 号：R965[医药卫生—药理学]