Rosuvastatin attenuates monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling and asymmetric dimethylarginine metabolism
Rosuvastatin attenuates monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling and asymmetric dimethylarginine metabolism
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DOI：
10.1016/j.ejphar.2011.05.035
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发表时间：
2011-09-01
影响因子：
5
通讯作者：
Dai, Guidong
中科院分区：
文献类型：
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作者：
Pei, Yingzi;Ma, Ping;Dai, Guidong
本研究旨在探讨瑞舒伐他汀能否通过调节Akt/eNOS信号通路和不对称二甲基精氨酸(ADMA)代谢来减轻野百合碱诱导的大鼠肺动脉高压。单剂量注射野百合碱(60 mg/kg)后，口服瑞舒伐他汀(5 mg/kg)第1~28天(预防性给药)或第15~28天(治疗性给药)，或以载药剂为对照。野百合碱治疗28d后，以肺动脉内膜增厚、右室肥厚和右心衰竭为特征的大鼠出现明显的肺动脉高压。瑞舒伐他汀(5 mg/kg，连续14天和28天)治疗可明显减轻野百合碱所致的肺血管重构、右室肥厚和功能障碍，并使下调的肺Akt/p-Akt和eNOS/p-eNOS表达正常化，同时增加DDAH2表达并降低血清ADMA水平。然而，PRMT1和GSK3β/p-GSK3β的表达在所有组之间没有差异(均P>；0.05)。结论：瑞舒伐他汀通过使Akt、eNOS和DDAH2表达正常化，降低ADMA水平，从而抑制野百合碱所致的肺动脉高压。(C)2011爱思唯尔B.V.保留所有权利。
This study was designed to investigate whether rosuvastatin could attenuate monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling pathway and asymmetric dimethylarginine (ADMA) metabolism in rats. After a single-dose injection of monocrotaline (60 mg/kg), oral administration of rosuvastatin (5 mg/kg) was started from day 1 to day 28 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. 28 days after monocrotaline, significant pulmonary hypertension characterized by pulmonary arterial medial wall thickening, right ventricular hypertrophy and right heart failure was observed. Rosuvastatin (5 mg/kg, for 14 days and 28 days) treatment significantly attenuated monocrotaline-induced pulmonary vascular remodeling, right ventricular hypertrophy and dysfunction, and normalized the down-regulated pulmonary Akt/p-Akt and eNOS/p-eNOS expressions, while increased DDAH2 expression accompanied by decreased serum level of ADMA. However expression of PRMT1 and GSK3 beta/p-GSK3 beta did not differ among all groups (all P>0.05). We concluded that rosuvastatin inhibits monocrotaline-induced pulmonary hypertension through normalization of Akt, eNOS and DDAH2 expressions, and decreasing the level of ADMA. (C) 2011 Elsevier B.V. All rights reserved.