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氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响
引用本文:王寒明,;王韵,;李雪芹,;白洋,;王怀良.氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响[J].解剖科学进展,2014(4):329-332.
作者姓名:王寒明  ;王韵  ;李雪芹  ;白洋  ;王怀良
作者单位:[1]辽宁医学院药理学教研室,辽宁锦州121001; [2]中国医科大学药学院临床药理教研室,辽宁沈阳110001; [3]中山市人民医院药学部,广东中山528403
基金项目:国家自然科学基金资助项目(No.81273511);辽宁省科技厅博士启动基金项目(No.20131066)
摘    要:目的研究氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响。方法建立野百合碱-1-1诱导的肺动脉高压大鼠模型,将大鼠随机分为4组:对照组、野百合碱组、氟西汀低剂量(2mg·kg·d)组、-1-1氟西汀高剂量(10mg·kg·d)组。观察各组大鼠血流动力学与肺小动脉形态学的变化,Western blot方法检测ROCK1与ROCK2的蛋白表达,以及MYPT1的磷酸化。结果野百合碱诱导大鼠肺动脉压力升高、肺动脉重构、肺组织炎症反应,上调大鼠肺组织中ROCK1与ROCK2以及增加Rho激酶的活性;氟西汀剂量依赖地抑制这些改变。结论氟西汀抑制野百合碱诱导的大鼠肺动脉高压,与抑制Rho激酶活性有关。

关 键 词:Rho激酶  肺动脉高压  氟西汀  野百合碱  大鼠

Involvement of Rho kinase activity in the protective effect of fluoxetine against monocrotaline-induced pulmonary arterial hypertension in rats
Institution:WANG Han-ming, WANG Yun, LI Xue-qin, BAI Yang, WANG Huai-liang( 1. Department of Pharmacology, Liaoning Medical College, Jinzhou 121001; 2. Depanent of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang 110001; 3. Department of Pharmacy, Zhongshan City People's Hospital, Zhongshan 528403, China )
Abstract:Objective To study the involvement of Rho kinase(ROCK) activity in the protective effect of fluoxetine against monocrotaline-induced pulmonary arterial hypertension in rats. Methods Monocrotaline was applied to establish pulmonary arterial hypertension in rats. The rats were randomly divided into four groups: control group,-1-1 monocrotaline group, low-dose fluoxetine group(2mg· kg d), and high-dose fluoxetine group(10). The hemodynamics and morphology of pulmonary arterioles were determined, and the expression of ROCK were measured by Western blot. Results Monocrotaline promoted the increase of pulmonary arterial pressure, pulmonary arterial remodeling and lung inflammation, and upregulated ROCK1 and ROCK2 protein expression and MYPT1 phosphorylation. Fluoxetine inhibited these changes dose dependently. Conclusion The inhibition of Fluoxetine on monocrotaline-induced pulmonary arterial hypertension might be related to the dowregulation of ROCK activity.
Keywords:Rho kinase  pulmonary arterial hypertention  fluoxetine  monocrotaline  rat
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